Database Query Results : , , Glycolysis

Glycolysis, Glycolysis: Click to Expand ⟱
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Glycolysis is a metabolic pathway that converts glucose into pyruvate, producing a small amount of ATP (energy) in the process. It is a fundamental process for cellular energy production and occurs in the cytoplasm of cells. In normal cells, glycolysis is tightly regulated and is followed by aerobic respiration in the presence of oxygen, which allows for the efficient production of ATP.
In cancer cells, however, glycolysis is often upregulated, even in the presence of oxygen. This phenomenon is known as the Warburg Mutations in oncogenes (like MYC) and tumor suppressor genes (like TP53) can alter metabolic pathways, promoting glycolysis and other anabolic processes that support cell growth.effect.
Acidosis: The increased production of lactate from glycolysis can lead to an acidic microenvironment, which may promote tumor invasion and suppress immune responses.

Glycolysis is a hallmark of malignancy transformation in solid tumor, and LDH is the key enzyme involved in glycolysis.

Pathways:
-GLUTs, HK2, PFK, PK, PKM2, LDH, LDHA, PI3K/AKT/mTOR, AMPK, HIF-1a, c-MYC, p53, SIRT6, HSP90α, GAPDH, HBT, PPP, Lactate Metabolism, ALDO

Natural products targeting glycolytic signaling pathways https://pmc.ncbi.nlm.nih.gov/articles/PMC9631946/
Alkaloids:
-Berberine, Worenine, Sinomenine, NK007, Tetrandrine, N-methylhermeanthidine chloride, Dauricine, Oxymatrine, Matrine, Cryptolepine

Flavonoids: -Oroxyline A, Apigenin, Kaempferol, Quercetin, Wogonin, Baicalein, Chrysin, Genistein, Cardamonin, Phloretin, Morusin, Bavachinin, 4-O-methylalpinumisofavone, Glabridin, Icaritin, LicA, Naringin, IVT, Proanthocyanidin B2, Scutellarin, Hesperidin, Silibinin, Catechin, EGCG, EGC, Xanthohumol.

Non-flavonoid phenolic compounds:
Curcumin, Resveratrol, Gossypol, Tannic acid.

Terpenoids:
-Cantharidin, Dihydroartemisinin, Oleanolic acid, Jolkinolide B, Cynaropicrin, Ursolic Acid, Triptolie, Oridonin, Micheliolide, Betulinic Acid, Beta-escin, Limonin, Bruceine D, Prosapogenin A (PSA), Oleuropein, Dioscin.

Quinones:
-Thymoquinone, Lapachoi, Tan IIA, Emodine, Rhein, Shikonin, Hypericin

Others:
-Perillyl alcohol, HCA, Melatonin, Sulforaphane, Vitamin D3, Mycoepoxydiene, Methyl jasmonate, CK, Phsyciosporin, Gliotoxin, Graviola, Ginsenoside, Beta-Carotene.
Scientific Papers found: Click to Expand⟱
2325- 2DG,    Research Progress of Warburg Effect in Hepatocellular Carcinoma
- Review, Var, NA
HK2↓, 2-Deoxyglucose (2-DG) is a widely studied HK2 inhibitor that has been reported to inhibit glycolysis by inhibiting hexokinase
Glycolysis↓,
PKM2↓, In rat HCC models, 2-DG was shown to reduce PKM2 and LDHA expression, leading to decreased aerobic glycolysis and tumor cell death
LDHA↓,
TumCD↑,
ChemoSen↑, Combining 2-DG with sorafenib demonstrated superior antitumor effects compared to sorafenib alone, suggesting its potential for synergistic action with other anticancer drugs
eff↑, Moreover, DHA combined with 2-DG can reportedly induce apoptosis in A549 and PC-9 cells

2327- 2DG,    2-Deoxy-d-Glucose and Its Analogs: From Diagnostic to Therapeutic Agents
- Review, Var, NA
Glycolysis↓, 2-DG inhibits glycolysis due to formation and intracellular accumulation of 2-deoxy-d-glucose-6-phosphate (2-DG6P), inhibiting the function of hexokinase and glucose-6-phosphate isomerase, and inducing cell death
HK2↓,
mt-ROS↑, 2-DG-mediated glucose deprivation stimulates reactive oxygen species (ROS) production in mitochondria, also leading to AMPK activation and autophagy stimulation.
AMPK↑,
PPP↓, 2-DG has been shown to block the pentose phosphate shunt
NADPH↓, Decreased levels of NADPH correlate with reduced glutathione levels, one of the major cellular antioxidants.
GSH↓,
Bax:Bcl2↑, Valera et al. also observed that in bladder cancer cells, 2-DG treatment modulates the Bcl-2/Bax protein ratio, driving apoptosis induction
Apoptosis↑,
RadioS↑, 2-DG radiosensitization results from its effect on thiol metabolism
eff↓, (NAC) treatment, downregulated glutamate cysteine ligase activity, or overexpression of ROS scavenging enzymes
Half-Life↓, its plasma half-life was only 48 min [117]) make 2-DG a rather poor drug candidate
other↝, Adverse effects of 2-DG administration in humans include fatigue, sweating, dizziness, and nausea, mimicking the symptoms of hypoglycemia
eff↓, Moreover, 2-DG has to be used at relatively high concentrations (≥5 mmol/L) in order to compete with blood glucose

2424- 2DG,  SRF,    The combination of the glycolysis inhibitor 2-DG and sorafenib can be effective against sorafenib-tolerant persister cancer cells
- in-vitro, HCC, Hep3B - in-vitro, HCC, HUH7
ChemoSen↓, combination of 2-DG and sorafenib reduced persister tumor growth in mice
Glycolysis↓, The glycolysis inhibitor 2-Deoxy-D-glucose (2-DG), an inhibitor of all forms of HK
HK1↓,
HK2↓,
ATP↓, reducing ATP production

1340- 3BP,    Safety and outcome of treatment of metastatic melanoma using 3-bromopyruvate: a concise literature review and case study
- Review, NA, NA
Glycolysis↓, inhibiting key glycolysis enzymes
HK2↓,
LDH↓,
OXPHOS↓, inhibits mitochondrial oxidative phosphorylation
angioG↓,
H2O2↑, induces hydrogen peroxide generation in cancer cells (oxidative stress effect)
eff↑, Concurrent use of a GSH depletor(paracetamol) with 3BP killed resistant melanoma cells

1341- 3BP,    The HK2 Dependent “Warburg Effect” and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate
- Review, NA, NA
Glycolysis↓, second-generation glycolysis inhibitor.
OXPHOS↓,
*toxicity↓, Normal cells remain unharmed
ROS↑, well known that this compound generates ROS
GSH↓,
eff↑, 3BP demonstrates synergistic activity with other compounds that reduce intracellular levels of GSH

5271- 3BP,    The anticancer agent 3-bromopyruvate: a simple but powerful molecule taken from the lab to the bedside
- Review, Var, NA
selectivity↑, 3-bromopyruvate (3BP), a simple alkylating chemical compound was presented to the scientific community as a potent anticancer agent, able to cause rapid toxicity to cancer cells without bystander effects on normal tissues.
selectivity↑, results obtained in cancer research with this small molecule have contradicted the just noted general fear. Indeed, a promising drug has been revealed with an effective mechanism of action and an outstanding selectivity towards cancer cells
ATP↓, once inside cancer cells 3BP can then inhibit both of their energy (ATP) producing systems, i.e., glycolysis, likely by inhibiting hexokinase-2 (hk-2) and mitochondrial oxidative phosphorylation
Glycolysis↓,
HK2↓,
mt-OXPHOS↓,
GAPDH↓, Different reports have shown that 3BP is able to inhibit GAPDH activity leading to the loss of the ATP-producing steps that occur downstream of this enzyme
mtDam↑, Mitochondria related cell death has also been reported following 3BP treatment.
GSH↓, Ehrke and co-workers have demonstrated that 3BP inhibits glycolysis and deplete the glutathione levels in primary rat astrocytes
ROS↑, Others have also observed an increase in ROS levels following 3BP treatment that induces endoplasmic reticulum stress
ER Stress↑,
TumAuto↑, Autophagy has been associated with 3BP activity in breast cancer cell lines (Zhang et al., 2014),
LC3‑Ⅱ/LC3‑Ⅰ↑, 3BP leads to aggressive autophagy involving a decrease in the ratio of LC3I/LC3II and the levels of p62 as well as dephosphorylation of Akt and p53.
p62↓,
Akt↓,
HDAC↓, 3BP’s, it has been reported to be involved in suppressing epigenetic events as it inhibits histone deacetylase (HDAC) isoforms 1 and 3 in MCF-7 breast cancer cells leading to apoptosis
TumCA↑, Proliferation inhibition by 3BP treatment has also been related with the induction of S-phase and G2/M- phase arrest (Liu et al. 2009)
Bcl-2↓, downregulation of the expression of Bcl-2, c-Myc and mutant p53, the upregulation of Bax, activation of caspase-3 and mitochondrial leakage of cytochrome c
cMyc↓,
Casp3↑,
Cyt‑c↑,
Mcl-1↓, mitochondria mediated apoptosis triggered by 3BP was found to be associated with the downregulation of Mcl-1 through the phosphoinositide-3-kinase/Akt pathway (Liu et al. 2014).
PARP↓, 3BP treatment decreases the levels of poly(ADP-ribose) polymerase (PARP) and cleaved PARP.
ChemoSen↑, it might be a good adjuvant for commonly used chemotherapy agents, or a replacement for such agents.

5281- 3BP,    A translational study “case report” on the small molecule “energy blocker” 3-bromopyruvate (3BP) as a potent anticancer agent: from bench side to bedside
- Case Report, Var, NA
Glycolysis↓, 3BP targets cancer cells’ energy metabolism, both its high glycolysis (“Warburg Effect”) and mitochondrial oxidative phosphorylation.
mt-OXPHOS↓,
ATP↓, This inhibits/ blocks total energy production leading to a depletion of energy reserves. Moreover, 3BP as an “Energy Blocker”, is very rapid in killing such cells.
selectivity↑, 3BP at its effective concentrations that kill cancer cells has little or no effect on normal cells.
toxicity↝, The results obtained hold promise for 3BP as a future cancer therapeutic without apparent cyto-toxicity when formulated properly.
OS↑, The patient (Fig. 5) was able to survive a much longer period than expected with an improved quality of life, which is clearly attributable to the treatment with 3BP.
QoL↑,

5282- 3BP,  Rad,    3-Bromopyruvate-mediated MCT1-dependent metabolic perturbation sensitizes triple negative breast cancer cells to ionizing radiation
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468
Glycolysis↓, Metabolomic analyses showed that 3BP causes inhibition of glycolysis
RadioS↑, Overall, MCT1-mediated metabolic perturbation in combination with radiotherapy is shown to be a promising strategy for the treatment of glycolytic tumors such as TNBC, overcoming the selectivity challenges of targeting glycolysis with glucose analogs
eff↑, 3BP is selectively toxic to cells expressing MCT1
GAPDH↓, 3BP inhibits GAPDH but not hexokinase
PPP↑, Pentose phosphate pathway is upregulated in response to 3BP
GSH↓, Glutathione and NADH are depleted at early time points
ECAR↓, prolonged incubation with 20 μM 3BP for 24 h resulted in a statistically significant selective decrease in ECAR

5277- 3BP,    3-Bromopyruvate inhibits pancreatic tumor growth by stalling glycolysis, and dismantling mitochondria in a syngeneic mouse model
- in-vivo, PC, Panc02
HK2↓, It exerts potent anticancer effects by inhibiting hexokinase II enzyme (HK2) of the glycolytic pathway in cancer cells while not affecting the normal cells.
selectivity↑, it doesn’t affect the normal cells but strongly toxic to cancer cells
ATP↓, 3-BP killed 95% of Panc-2 cells at 15 μM concentration and severely inhibited ATP production by disrupting the interaction between HK2 and mitochondrial Voltage Dependent Anion Channel-1 (VDAC1) protein.
mtDam↑, Electron microscopy data revealed that 3-BP severely damaged mitochondrial membrane in cancer cells.
Dose↝, We further examined therapeutic effect of 3-BP in syngeneic mouse pancreatic cancer model by treating animals with 10, 15 and 20 mg/kg dose. 3-BP at 15 & 20 mg/kg dose level significantly reduced tumor growth by approximately 75-80% in C57BL/6 female
TumCG↓, 3-BP inhibit in vivo pancreatic tumor growth in C57BL/6 mouse model
Casp3↑, observed enhanced expression of active caspase-3 in tumor tissues exhibited apoptotic death.
Glycolysis↓, Notably, metabolomic data also revealed severe inhibition in glycolysis, NADP, ATP and lactic acid production in cancer cells treated with 40 μM 3-BP.
NADPH↓,
ATP↓,
ROS↑, 3-BP treatment produces increased levels of reactive oxygen species (ROS), which causes DNA damage with reduction of free glutathione levels [11].
DNAdam↑,
GSH↓,
Bcl-2↓, Further, treatment with 40 µM of 3-BP suppressed BCL2L1 expression and causing activation of mitochondrial caspases
Casp↑,
lactateProd↓, Metabolic inhibition of glucose consumption and lactic acid production in cancer cells treated with 3-BP

5274- 3BP,    ME3BP-7 is a targeted cytotoxic agent that rapidly kills pancreatic cancer cells expressing high levels of monocarboxylate transporter MCT1
- in-vitro, PC, NA
eff↑, novel microencapsulated formulation of 3BP (ME3BP-7), which is effective against a variety of PDAC cells in vitro and remains stable in serum.
TumCG↓, Furthermore, systemically administered ME3BP-7 significantly reduces pancreatic cancer growth and metastatic spread in multiple orthotopic models of pancreatic cancer with manageable toxicity.
TumMeta↓,
toxicity↝,
Glycolysis↓, The anticancer effects of 3BP were initially attributed to inhibition of glycolysis (Ganapathy-Kanniappan et al., 2009;
toxicity↓, Our previous work demonstrated that microencapsulation of 3BP reduces its toxicity (Chapiro et al., 2014).
Dose↝, we were only able to reliably deliver multiple doses of the drug intravenously (i.v.), and the number of injections and time periods over which we could administer the drug were limited.

5272- 3BP,    The efficacy of the anticancer 3-bromopyruvate is potentiated by antimycin and menadione by unbalancing mitochondrial ROS production and disposal in U118 glioblastoma cells
- in-vitro, GBM, U87MG - in-vitro, Nor, HEK293
Glycolysis↓, We used the antiglycolytic 3-bromopyruvate (3BP) as a metabolic modifier to treat U118 glioblastoma cell
ROS↑, ROS generated in mitochondria were enhanced at 30 μM 3BP, possibly by unbalancing their generation and their disposal because of glutathione peroxidase inhibition.
GPx↓,
eff↓, Indeed, the scavenger of mitochondrial superoxide MitoTEMPO counteracted 3BP-induced cyt c release and weakened the potentiating effect of 3BP/
OXPHOS↓, (3BP) is a reactive non-specific drug that can act as a metabolic modifier by interfering with glycolysis and oxidative phosphorylation in cancer cells
HK2↓, The mitochondrial hexokinase-II is the main target since its activity is specifically blocked by the formation of a pyruvinyl adduct after reacting with 3BP at the surface of the outer mitochondrial membrane
ATP↓, In malignant tumour cell lines, 3BP inhibits ATPase activity, reduces ATP levels, and reverses chemoresistance by antagonizing drug efflux by acting on the ATP-binding cassette transporters (
ROS↑, Furthermore, 3BP increases the production of reactive oxygen species (ROS) (Ihrlund et al., 2008; Kim et al., 2008; Macchioni et al., 2011a), induces ER stress,
ER Stress↑,
BioAv↓, Unfortunately, prolonged treatment with the drug reduces ROS levels and confers resistance by inducing regulatory genes that act on antioxidant systems.
Cyt‑c↑, 3BP induces cytochrome c release without triggering an apoptotic cascade in U118 cells
eff↑, The ROS enhancers antimycin and menadione sensitize U118 cells to 3BP

5257- 3BP,    Tumor Energy Metabolism and Potential of 3-Bromopyruvate as an Inhibitor of Aerobic Glycolysis: Implications in Tumor Treatment
- Review, Var, NA
Glycolysis↓, In recent years, a small molecule alkylating agent, 3-bromopyruvate (3-BrPA), being an effective glycolytic inhibitor, has shown great potential as a promising antitumor drug.
mt-OXPHOS↓, Not only it targets glycolysis process, but also inhibits mitochondrial OXPHOS in tumor cells.
HK2↓, The direct inhibition of mitochondrial HK-II isolated from the rabbit liver implanted VX2 tumor via 3-BrPA was demonstrated by Ko et al. [17].
Cyt‑c↑, -BrPA treatment resulted in an increase of cytochrome c release [59,60], along with an elevated expression of active proapoptotic caspase-3 and a decrease of antiapoptotic Bcl-2 and Mcl-1 [59]
Casp3↓,
Bcl-2↓,
Mcl-1↓,
GAPDH↓, Additionally, GAPDH was found to be inhibited by 3-BrPA in several studies
LDH↓, Recent reports showed 3-BrPA had ability to inhibit post glycolysis targets and other metabolic pathways, such as LDH, PDH, TCA cycle, and glutaminolysis
PDH↓, 3-BrPA was proven to be an inhibitor of PDH [72,73,74],
TCA↓,
GlutaM↓, this inhibition of TCA cycle can lead to the impairment of glutaminolysis due to α-KG generated from glutamine is incorporated into the TCA cycle by IDH and αKD activities
GSH↓, Indeed, a remarkable decrease of reduced glutathione (GSH) level was observed after 3-BrPA treatment in both microorganisms and various tumor cells [53,61,65].
ATP↓, 3-BrPA successfully killed AS-30D hepatocellular carcinoma (HCC) cells via the inhibition of both ATP-producing glycolysis and mitochondrial respiration [17].
mitResp↓,
ROS↑, the increase of ROS and concomitant decrease of GSH were commonly found in 3-BrPA-mediated antitumor studies [53,59,61,64,65,76,77,86,89].
ChemoSen↑, When 3-BrPA was combined with cisplatin or oxaliplatin with non-toxic low-dose, 3-BrPA strikingly enhanced the antiproliferative effects of both platinum drugs in HCT116 cells and resistant p53-deficient HCT116 cells [89].
toxicity↝, Finally, two years after the first diagnosis, the patient died due to an overload of liver function rather than the tumor itself [118].

5258- 3BP,    3-bromopyruvate: Targets and outcomes
- Review, Var, NA
Glycolysis↓, The pyruvate mimetic 3-bromopyruvate (3-BP) is generally presented as an inhibitor of glycolysis and has shown remarkable efficacy in not only preventing tumor growth, but even eradicating existant tumors in animal studies.
TumCG↓,

5269- 3BP,    The anti-metabolite KAT/3BP has in vitro and in vivo anti-tumor activity in lymphoma models.
- in-vitro, HCC, NA
toxicity↑, 3-Bromopyruvate (3BP), a small alkylating agent, acts as an anti-metabolite to vital substrates in cancer metabolism and exhibits antitumor activity across various cancer types, but the unformulated 3BP can cause high toxicity
eff↝, This study explores the efficacy of the 3BP clinical derivative KAT/3BP, currently in phase 1 for patients with hepatocellular carcinoma, in lymphoma models.
eff↑, AT/3BP exhibited synergistic activity when combined with lymphoma therapies, including bendamustine and R-CHOP.
Glycolysis↓, At acidic extracellular pH, 3BP enters cancer cells via monocarboxylic acid-1 (MCT-1) and inhibits glycolysis through hexokinase II (HK-2) covalent modification
HK2↓, with HK-2 inhibition and dissociation from mitochondria, apoptosis-inducing factor (AIF) release, and apoptosis induction (9).
AIF↑,
Apoptosis↑,
NK cell↑, In the latter, tumor growth was in vivo reversed, with an increase in the number of circulating CD4+, CD8+, and NK- cells
toxicity↑, unformulated 3BP administrations are associated with severe toxicities, including deaths (22,23)
toxicity↓, However, improvements have been made in developing novel 3BP formulations based on liposomes, polyethylene glycol (PEG), PEGylated liposomes (stealth liposomes), perillyl alcohol formulations, and others (12,22,24
Dose↝, KAT-101 and KAT-201 are two clinical 3BP derivatives formulated for oral or intratumoral (IT) administration, respectively (National Cancer Institute Thesaurus Codes C193479 and C193479), now entering the early clinical evaluation of patients with h
AntiTum↑, KAT/3BP has in vivo antitumor activity in a syngeneic mouse model.

5264- 3BP,    Candidate cancer drug suspected after death of three patients at an alternative medicine clinic
- Review, Var, NA
toxicity↑, German police took action on 4 August after two patients from the Netherlands and one from Belgium died shortly after undergoing treatment at the Biological Cancer Centre, run by alternative practitioner Klaus Ross in the town of Brüggen, Germany
Glycolysis↓, It is believed to "starve" tumor cells to death by inhibiting glycolysis, the breakdown of glucose molecules to provide cells with energy.
eff↑, experiments on human cancer cell lines showed that combining another chemotherapeutic with 3BP increased its efficacy.
OS↑, the patient "was able to survive a much longer period than expected with an improved quality of life, which is clearly attributable to the treatment with 3BP,
QoL↑,
toxicity↝, Vogl says doctors should "absolutely" not perform systemic infusions, in which the drug circulates through the entire body. "

5265- 3BP,    KAT/3BP: A Metabolism-Targeting Agent with Single and Combination Activity in Aggressive B-Cell Lymphomas
- Review, lymphoma, NA
Glycolysis↓, Under acidic extracellular pH, 3BP is transported into cancer cells via monocarboxylate transporter 1 (MCT1), inhibiting glycolysis by covalently modifying hexokinase II (HK2).
HK2↓, HK2 dissociation from mitochondria, release of apoptosis-inducing factor (AIF), and induction of apoptosis
AIF↓,
Apoptosis↑,
NK cell↑, In the latter, tumor regression was accompanied by increased circulating CD4+, CD8+, and NK cells, enhanced tumor-associated macrophage infiltration, and reduced local immunosuppression

5266- 3BP,    3-bromopyruvate-based agent KAT-101
- Review, Var, NA
eff↑, Upon oral administration of 3-BP-based agent KAT-101, the 3-BP derivative, being structurally similar to lactic acid, specifically binds to and enters cancer cells through monocarboxylic acid transporters (MCTs)
Glycolysis↓, KAT-101 interferes with both glycolysis and mitochondrial oxidative phosphorylation (OxPhos), thereby depleting adenosine triphosphate (ATP) levels and thus limits energy supply needed by cancer cells to proliferate.
OXPHOS↓,
ATP↓,
TumCP↓,
Apoptosis↑, This induces cancer cell apoptosis and prevents cancer cell proliferation.
HK2↓, In addition, KAT-101 is able to release mitochondrial-bound hexokinase (HK) II (HK2)
MPT↑, increases the formation of mitochondrial permeability transition pores (MPTPs), which induces apoptosis.
LDH↓, KAT-101 also inhibits a variety of enzymes, including lactate dehydrogenase (LDH), pyruvate dehydrogenase (PDH) and pyruvate dehydrogenase kinase (PDHK).
PDH↓,

3452- 5-ALA,    5-ALA Is a Potent Lactate Dehydrogenase Inhibitor but Not a Substrate: Implications for Cell Glycolysis and New Avenues in 5-ALA-Mediated Anticancer Action
- in-vitro, GBM, T98G - in-vitro, GBM, LN-18 - in-vitro, GBM, U87MG
Glycolysis↓, we found that 5-ALA, a natural precursor of heme, can hinder cell glycolysis, which is the main path of energy production for most cancer cells.
LDH↓, ore specifically, we found that 5-ALA can block an enzyme involved in glycolysis, called lactate dehydrogenase (LDH)
eff↝, We found that 5-ALA has a potency of LDH inhibition comparable to other established LDH inhibitors, such as oxamate or tartronic acid
ECAR↓, a marked decrease in extracellular acidification rate (ECAR) was registered as a consequence of administering 5-ALA,

5468- AF,    The gold complex auranofin: new perspectives for cancer therapy
- Review, Var, NA
TrxR↓, Auranofin mainly targets the anti-oxidative system catalyzed by thioredoxin reductase (TrxR), which protects the cell from oxidative stress and death in the cytoplasm and the mitochondria.
ROS↑, Inhibiting TrxR dysregulates the intracellular redox state causing increased intracellular reactive oxygen species levels, and stimulates cellular demise
eff↑, TrxR is over-expressed in many cancers as an adaptive mechanism for cancer cell proliferation, rendering it an attractive target for cancer therapy, and auranofin as a potential therapeutic agent for cancer.
Apoptosis↑, promotion of ASK-induced apoptosis, and blockage of cell growth, proliferation, and survival due to reduced AKT activity and NF-kB- and p53-mediated transcription.
TumCG↓,
TumCP↓,
Akt↓,
NF-kB↓,
DNAdam↑, DNA damage
eff↝, auranofin inhibits TrxR1 in a p53-independent manner
eff↓, Pre-treatment with NAC counteracted the cancer cell killing effects of auranofin,
PI3K↓, auranofin induces cytotoxicity in human pancreatic adenocarcinoma and non-small cell lung cancer via the inhibition of the PI3K/AKT/mTOR pathway
Akt↓,
mTOR↓,
Hif1a↓, auranofin inhibits the cancer cell response to hypoxia, demonstrated by a decrease in HIF-1 𝛼 expression and VEGF secretion upon auranofin treatment under hypoxic conditions
VEGF↓,
Casp3↑, auranofin was shown to induce caspase-3-mediated apoptosis in human ovarian carcinoma SKOV-3 cells
CSCs↓,
ATP↓, it was found that auranofin inhibits ABCG2 function by depleting cellular ATP via inhibition of glycolysis [96]
Glycolysis↓,
eff↑, auranofin synergizes with another Trx1 inhibitor, piperlongumine, in killing gastric cancer cells in association with ROS-mediated ER stress response and mitochondrial dysfunction.
eff↑, when the gold complex is combined with either selenite or tellurite [104]
MMP↓, Increased ROS induced by AUR causes decreased membrane potential in the mitochondrial membrane, resulting in a decrease in anti-apoptotic proteins, caspase-dependent cell death, and translocation of apoptosis-inducing factor (AIF)
AIF↑,
toxicity↓, Auranofin is considered safe for human use in treating rheumatoid arthritis; thus, this gold derivative can reach the clinic for other diseases relatively quickly and at a low cost

944- AG,    Astragalus saponins inhibit cell growth, aerobic glycolysis and attenuate the inflammatory response in a DSS-induced colitis model
- vitro+vivo, CRC, NA
Glycolysis↓,
lactateProd↓,
TumCG↓,

5165- AL,    The human allicin-proteome: S-thioallylation of proteins by the garlic defence substance allicin and its biological effects
- in-vitro, AML, Jurkat - in-vitro, Nor, L929
necrosis↑, Allicin induces apoptosis or necrosis in a dose-dependent manner but biocompatible doses influence cellular metabolism and signalling cascades.
Thiols↓, Oxidation of protein thiols and depletion of the glutathione pool are thought to be responsible for allicin's physiological effects.
GSH↓,
ENO1↓, allicin caused inhibition of enolase activity, an enzyme considered a cancer therapy target.
Zn2+↑, Allicin leads to Zn2+ release in murine EL-4 cells
Glycolysis↓, suggests that allicin can inhibit glycolysis which provides electron donors for ATP generation required for cellular biosynthesis pathways and growth of the cells.
ATP↓,
BioAv↓, achieving therapeutically relevant concentrations of allicin via the oral route is therefore unlikely and more direct routes of application to the desired site of action need to be considered

3434- ALA,    Alpha lipoic acid modulates metabolic reprogramming in breast cancer stem cells enriched 3D spheroids by targeting phosphoinositide 3-kinase: In silico and in vitro insights
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
tumCV↓, significant dose-dependent reduction in cell viability, with the half-maximal inhibitory concentration (IC50) of LA to be 3.2 mM for MCF-7 cells and 2.9 mM for MDA-MB-231 cells
PI3K↓, LA significantly inhibited PI3K, p-AKT, p-p70S6K and p-mTOR levels
p‑Akt↓,
p‑P70S6K↓,
mTOR↓,
ATP↓, LA markedly reduced both ATP levels and glucose uptake (Fig. 4A and 4B). LA also induced ROS generation in both MCF-7 and MDA-MB231 spheroids
GlucoseCon↓,
ROS↑,
PKM2↓, LA downregulated the expression of PKM2 and LDHA in the spheroids, indicating an inhibition of glycolysis in BCSCs
LDHA↓,
Glycolysis↓,
ChemoSen↑, LA enhances chemosensitivity of spheroids to Dox treatment

3436- ALA,    Alpha lipoic acid modulates metabolic reprogramming in breast cancer stem cells enriched 3D spheroids by targeting phosphoinositide 3-kinase: In silico and in vitro insights Author links open overlay panel
- in-vitro, BC, MCF-7
ChemoSen↑, LA also enhanced the sensitivity of breast cancer spheroids to doxorubicin (Dox), demonstrating a synergistic effect.
PI3K↓, LA inhibits PI3K/AKT signaling in breast cancer spheroids
Akt↓,
ATP↓, found that LA markedly reduced both ATP levels and glucose uptake
GlucoseCon↓,
ROS↑, LA also induced ROS generation in both MCF-7 and MDA-MB231 spheroids
PKM2↓, LA downregulated the expression of PKM2 and LDHA in the spheroids, indicating an inhibition of glycolysis in BCSCs
Glycolysis↓,
CSCs↓,
IGF-1R↓, LA inhibits IGF-1R via furin downregulation, synergizes with other anticancer drugs like paclitaxel and cisplatin, and enhances radiosensitivity in breast cancer
Furin↓,
RadioS↑,

3441- ALA,    α-Lipoic Acid Maintains Brain Glucose Metabolism via BDNF/TrkB/HIF-1α Signaling Pathway in P301S Mice
- in-vivo, AD, NA
*tau↓, α-lipoic acid (LA), which is a naturally occurring cofactor in mitochondrial, has been shown to have properties that can inhibit the tau pathology and neuronal damage in our previous research
*GlucoseCon↑, chronic LA administration significantly increased glucose availability by elevating glucose transporter 3 (GLUT3), GLUT4, vascular endothelial growth factor (VEGF) protein and mRNA level, and heme oxygenase-1 (HO-1) protein level in P301S mouse brain
*GLUT3↑,
*GLUT4↑,
*VEGF↑,
*HO-1↑,
*Glycolysis↑, LA also promoted glycolysis by directly upregulating hexokinase (HK) activity, indirectly by increasing proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and DNA repair enzymes (OGG1/2 and MTH1).
*HK1↑, Our results indicated that the activity of HK was significantly increased after 10 mg/kg LA treatment.
*PGC-1α↑,
*Hif1a↑, found the underlying mechanism of restored glucose metabolism might involve in the activation of brain-derived neurotrophic factor (BDNF)/tyrosine Kinase receptor B (TrkB)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway by LA treatment.
*neuroP↑,

3443- ALA,    Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention
- Review, Var, NA - Review, AD, NA
*antiOx↑, antioxidant potential and free radical scavenging activity.
*ROS↓,
*IronCh↑, Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E.
*cognitive↑, α-Lipoic acid enantiomers and its reduced form have antioxidant, cognitive, cardiovascular, detoxifying, anti-aging, dietary supplement, anti-cancer, neuroprotective, antimicrobial, and anti-inflammatory properties.
*cardioP↓,
AntiCan↑,
*neuroP↑,
*Inflam↓, α-Lipoic acid can reduce inflammatory markers in patients with heart disease
*BioAv↓, bioavailability in its pure form is low (approximately 30%).
*AntiAge↑, As a dietary supplements α-lipoic acid has become a common ingredient in regular products like anti-aging supplements and multivitamin formulations
*Half-Life↓, it has a half-life (t1/2) of 30 min to 1 h.
*BioAv↝, It should be stored in a cool, dark, and dry environment, at 0 °C for short-term storage (few days to weeks) and at − 20 °C for long-term storage (few months to years).
other↝, Remarkably, neither α-lipoic acid nor dihydrolipoic acid can scavenge hydrogen peroxide, possibly the most abundant second messenger ROS, in the absence of enzymatic catalysis.
EGFR↓, α-Lipoic acid inhibits cell proliferation via the epidermal growth factor receptor (EGFR) and the protein kinase B (PKB), also known as the Akt signaling, and induces apoptosis in human breast cancer cells
Akt↓,
ROS↓, α-Lipoic acid tramps the ROS followed by arrest in the G1 phase of the cell cycle and activates p27 (kip1)-dependent cell cycle arrest via changing of the ratio of the apoptotic-related protein Bax/Bcl-2
TumCCA↑,
p27↑,
PDH↑, α-Lipoic acid drives pyruvate dehydrogenase by downregulating aerobic glycolysis and activation of apoptosis in breast cancer cells, lactate production
Glycolysis↓,
ROS↑, HT-29 human colon cancer cells; It was concluded that α-lipoic acid induces apoptosis by a pro-oxidant mechanism triggered by an escalated uptake of mitochondrial substrates in oxidizable form
*eff↑, Several studies have found that combining α-lipoic acid and omega-3 fatty acids has a synergistic effect in slowing functional and cognitive decline in Alzheimer’s disease
*memory↑, α-lipoic acid inhibits brain weight loss, downregulates oxidative tissue damage resulting in neuronal cell loss, repairs memory and motor function,
*motorD↑,
*GutMicro↑, modulates the gut microbiota without reducing the microbial diversity (

3454- ALA,    Lipoic acid blocks autophagic flux and impairs cellular bioenergetics in breast cancer and reduces stemness
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
TumCG↑, Lipoic acid inhibits breast cancer cell growth via accumulation of autophagosomes.
Glycolysis↓, Lipoic acid inhibits glycolysis in breast cancer cells.
ROS↑, Lipoic acid induces ROS production in breast cancer cells/BCSC.
CSCs↓, Here, we demonstrate that LA inhibits mammosphere formation and subpopulation of BCSCs
selectivity↑, In contrast, LA at similar doses. had no significant effect on the cell viability of the human embryonic kidney cell line (HEK-293)
LC3B-II↑, LA treatment (0.5 mM and 1.0 mM) increased the expression level of LC3B-I to LC3B-II in both MCF-7 and MDA-MB231cells at 48 h
MMP↓, LA induced mitochondrial ROS levels, decreased mitochondria complex I activity, and MMP in both MCF-7 and MDA-MB231 cells
mitResp↓, In MCF-7 cells, we found a substantial reduction in maximal respiration and ATP production at 0.5 mM and 1 mM of LA treatment after 48 h
ATP↓,
OCR↓, LA at 2.5 mM decreased OCR
NAD↓, we found that LA (0.5 mM and 1 mM) significantly reduced ATP production and NAD levels in MCF-7 and MDA-MB231 cells
p‑AMPK↑, LA treatment (0.5 mM and 1.0 mM) increased p-AMPK levels;
GlucoseCon↓, LA (0.5 mM and 1 mM) significantly decreased glucose uptake and lactate production in MCF-7, whereas LA at 1 mM significantly reduced glucose uptake and lactate production in MDA-MB231 cells but it had no effect at 0.5 mM
lactateProd↓,
HK2↓, LA reduced hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA) expression in MCF-7 and MDA-MB231 cells
PFK↓,
LDHA↓,
eff↓, Moreover, we found that LA-mediated inhibition of cellular bioenergetics including OCR (maximal respiration and ATP production) and glycolysis were restored by NAC treatment (Fig. 6E and F) which indicates that LA-induced ROS production is responsibl
mTOR↓, LA inhibits mTOR signaling and thereby decreased the p-TFEB levels in breast cancer cells
ECAR↓, LA also inhibits glycolysis as evidenced by decreased glucose uptake, lactate production, and ECAR.
ALDH↓, LA decreased ALDH1 activity, CD44+/CD24-subpopulation, and increased accumulation of autophagosomes possibly due to inhibition of autophagic flux of breast cancer.
CD44↓,
CD24↓,

2319- Api,    Apigenin sensitizes radiotherapy of mouse subcutaneous glioma through attenuations of cell stemness and DNA damage repair by inhibiting NF-κB/HIF-1α-mediated glycolysis
- in-vitro, GBM, NA
Glycolysis↓, Apigenin inhibited the activities of glycolytic enzymes and expressions of nuclear factor kappa B (NF-κB) p65, hypoxia inducible factor-lα (HIF-1α), glucose transporter (GLUT)-1/3 and pyruvate kinase isozyme type M2 (PKM2) proteins in tumor tissues.
NF-kB↓,
p65↓,
Hif1a↓,
GLUT1↓,
GLUT3↓,
PKM2↓,
RadioS↑, Apigenin sensitizes the radiotherapy of SU3-5R cells-inoculated subcutaneous glioma
TumVol↓, Moreover, the tumor weight and relative tumor weight in the three treatment groups were significantly lower than those in the control group
TumW↓,

2299- Api,    Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
- Review, Var, NA
TumCP↓, apigenin reduced proliferation and angiogenesis and significantly suppressed the mRNA and protein expression of HIF-1α, VEGF, and GLUT1 under normoxic and hypoxic conditions
angioG↓,
Hif1a↓,
VEGF↓,
GLUT1↓,
PKM2↓, Moreover, apigenin was suggested to be an allosteric inhibitor of PKM2 due to its ability to ensure a low PKM2/PKM1 ratio and restrain proliferation of colon cancer (HCT116) cells through a blockade of PKM2-dependent glycolysis
Glycolysis↓,

2316- Api,    The interaction between apigenin and PKM2 restrains progression of colorectal cancer
- in-vitro, CRC, LS174T - in-vitro, CRC, HCT8 - in-vivo, CRC, NA
TumCP↓, the results proved that the anti-CRC activity of apigenin was positively correlated with pyruvate kinase M2 (PKM2) expression, characterized by the inhibition of cell proliferation and increase of apoptotic effects induced by apigenin in LS-174T cell
PKM2↓, findings reveal that apigenin is worthy of consideration as a promising PKM2 inhibitor for the prevention of CRC
Glycolysis↓, Apigenin restricted the glycolysis of LS-174T and HCT-8 cells by targeting the K433 site of PKM2, thereby playing an anti-CRC role in vivo and in vitro
TumCG↑, apigenin markedly attenuated tumor growth without any adverse effects.
selectivity↑,

2314- Api,    Apigenin Restrains Colon Cancer Cell Proliferation via Targeted Blocking of Pyruvate Kinase M2-Dependent Glycolysis
- in-vitro, Colon, HCT116 - in-vitro, Colon, HT29 - in-vitro, Colon, DLD1
Glycolysis↓, AP could block cellular glycolysis through restraining the tumor-specific pyruvate kinase M2 (PKM2) activity and expression and further significantly induce anti-colon cancer effects.
PKM2:PKM1↓,
β-catenin/ZEB1↓, AP decreases the expression of PKM2 in HCT116 by blocking the B-catenin/c-Myc /PTBP1 pathway
cMyc↓,

206- Api,    Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress
- in-vitro, Lung, H1299 - in-vitro, Lung, H460 - in-vitro, Lung, A549 - in-vitro, CRC, HCT116 - in-vitro, Melanoma, A375 - in-vitro, Lung, H2030 - in-vitro, CRC, SW480
Glycolysis↓, glucose consumption, lactate production, and ATP production were all strongly decreased by apigenin
lactateProd↓,
PGK1↓,
ALDOA↓,
GLUT1↓, Apigenin reduces GLUT1 expression levels.
ENO1↓,
ATP↓,
Casp9↑,
Casp3↑,
cl‑PARP↑, cleavage
PI3K/Akt↓,
HK1↓, HK1, HK2
HK2↓,
ROS↑, Apigenin causes oxidative stress leading to apoptosis. Because apoptotic signal transduction cascades involving caspase-9, -3 and PARP cleavage can be activated by increased ROS levels
Apoptosis↑,
eff↓, Cancer cells expressing high levels of GLUT1 are resistant to apigenin-induced apoptosis through metabolic compensation of glucose utilization.
NADPH↓, apigenin significantly decreased glucose utilization through suppression of GLUT1 expression, and consequently decreased NADPH production, which led to increased ROS levels.
PPP↓, inhibition of the PPP

3383- ART/DHA,    Dihydroartemisinin: A Potential Natural Anticancer Drug
- Review, Var, NA
TumCP↓, DHA exerts anticancer effects through various molecular mechanisms, such as inhibiting proliferation, inducing apoptosis, inhibiting tumor metastasis and angiogenesis, promoting immune function, inducing autophagy and endoplasmic reticulum (ER) stres
Apoptosis↑,
TumMeta↓,
angioG↓,
TumAuto↑,
ER Stress↑,
ROS↑, DHA could increase the level of ROS in cells, thereby exerting a cytotoxic effect in cancer cells
Ca+2↑, activation of Ca2+ and p38 was also observed in DHA-induced apoptosis of PC14 lung cancer cells
p38↑,
HSP70/HSPA5↓, down-regulation of heat-shock protein 70 (HSP70) might participate in the apoptosis of PC3 prostate cancer cells induced by DHA
PPARγ↑, DHA inhibited the growth of colon tumor by inducing apoptosis and increasing the expression of peroxisome proliferator-activated receptor γ (PPARγ)
GLUT1↓, DHA was shown to inhibit the activity of glucose transporter-1 (GLUT1) and glycolytic pathway by inhibiting phosphatidyl-inositol-3-kinase (PI3K)/AKT pathway and downregulating the expression of hypoxia inducible factor-1α (HIF-1α)
Glycolysis↓, Inhibited glycolysis
PI3K↓,
Akt↓,
Hif1a↓,
PKM2↓, DHA could inhibit the expression of PKM2 as well as inhibit lactic acid production and glucose uptake, thereby promoting the apoptosis of esophageal cancer cells
lactateProd↓,
GlucoseCon↓,
EMT↓, regulating the EMT-related genes (Slug, ZEB1, ZEB2 and Twist)
Slug↓, Downregulated Slug, ZEB1, ZEB2 and Twist in mRNA level
Zeb1↓,
ZEB2↓,
Twist↓,
Snail?, downregulated the expression of Snail and PI3K/AKT signaling pathway, thereby inhibiting metastasis
CAFs/TAFs↓, DHA suppressed the activation of cancer-associated fibroblasts (CAFs) and mouse cancer-associated fibroblasts (L-929-CAFs) by inhibiting transforming growth factor-β (TGF-β signaling
TGF-β↓,
p‑STAT3↓, blocking the phosphorylation of STAT3 and polarization of M2 macrophages
M2 MC↓,
uPA↓, DHA could inhibit the growth and migration of breast cancer cells by inhibiting the expression of uPA
HH↓, via inhibiting the hedgehog signaling pathway
AXL↓, DHA acted as an Axl inhibitor in prostate cancer, blocking the expression of Axl through the miR-34a/miR-7/JARID2 pathway, thereby inhibiting the proliferation, migration and invasion of prostate cancer cells.
VEGFR2↓, inhibition of VEGFR2-mediated angiogenesis
JNK↑, JNK pathway activated and Beclin 1 expression upregulated.
Beclin-1↑,
GRP78/BiP↑, Glucose regulatory protein 78 (GRP78, an ER stress-related molecule) was upregulated after DHA treatment.
eff↑, results demonstrated that DHA-induced ER stress required iron
eff↑, DHA was used in combination with PDGFRα inhibitors (sunitinib and sorafenib), it could sensitize ovarian cancer cells to PDGFR inhibitors and achieved effective therapeutic efficacy
eff↑, DHA combined with 2DG (a glycolysis inhibitor) synergistically induced apoptosis through both exogenous and endogenous apoptotic pathways
eff↑, histone deacetylase inhibitors (HDACis) enhanced the anti-tumor effect of DHA by inducing apoptosis.
eff↑, DHA enhanced PDT-induced cell growth inhibition and apoptosis, increased the sensitivity of esophageal cancer cells to PDT by inhibiting the NF-κB/HIF-1α/VEGF pathway
eff↑, DHA was added to magnetic nanoparticles (MNP), and the MNP-DHA has shown an effect in the treatment of intractable breast cancer
IL4↓, downregulated IL-4;
DR5↑, Upregulated DR5 in protein, Increased DR5 promoter activity
Cyt‑c↑, Released cytochrome c from the mitochondria to the cytosol
Fas↑, Upregulated fas, FADD, Bax, cleaved-PARP
FADD↑,
cl‑PARP↑,
cycE/CCNE↓, Downregulated Bcl-2, Bcl-xL, procaspase-3, Cyclin E, CDK2 and CDK4
CDK2↓,
CDK4↓,
Mcl-1↓, Downregulated Mcl-1
Ki-67↓, Downregulated Ki-67 and Bcl-2
Bcl-2↓,
CDK6↓, Downregulated of Cyclin E, CDK2, CDK4 and CDK6
VEGF↓, Downregulated VEGF, COX-2 and MMP-9
COX2↓,
MMP9↓,

2322- ART/DHA,    Dihydroartemisinin Regulates Self-Renewal of Human Melanoma-Initiating Cells by Targeting PKM2/LDHARelated Glycolysis
- in-vitro, Melanoma, NA
TumCP↓, DHA inhibits the proliferation of melanoma cells and blocks the cell cycle process.
PKM2↓, DHA reduces ATP production and downregulate PKM2 and LDHA activities without regulating the expression of the PKM2 and LDHA proteins in melanoma cells
LDHA↓,
Glycolysis↓, downregulates glucose metabolism in melanoma cells.

2320- ART/DHA,    Dihydroartemisinin Inhibits the Proliferation of Leukemia Cells K562 by Suppressing PKM2 and GLUT1 Mediated Aerobic Glycolysis
- in-vitro, AML, K562 - in-vitro, Liver, HepG2
Glycolysis↓, DHA prevented cell proliferation in K562 cells through inhibiting aerobic glycolysis.
GlucoseCon↓, Lactate product and glucose uptake were inhibited after DHA treatment.
lactateProd↓,
GLUT1↓, DHA modulates glucose uptake through downregulating glucose transporter 1 (GLUT1) in both gene and protein levels.
PKM2↓, DHA treatment, decreased expression of PKM2 was confirmed in situ.
ECAR↓, ECAR parameters including the glycolytic activity and capacity decreased in a concentration-dependent manner in K562 cells following DHA administration
LDHA↓, DHA treatment downregulated the relative expression of GLUT1, PKM2, LDH-A and c-Myc
cMyc↓,
other↝, The relative changes of PDK1, P53, HIF-1α, HK2, and PFK1 expression were modest, with most genes being altered by less than 2-fold

2324- ART/DHA,    Research Progress of Warburg Effect in Hepatocellular Carcinoma
- Review, Var, NA
PKM2↓, DHA effectively suppressed aerobic glycolysis and ESCC progression by downregulating PKM2 expression in esophageal squamous cell carcinoma (ESCC) and ESCC cells
GLUT1↓, DHA inhibited leukemia cell K562 proliferation by suppressing GLUT1 and PKM2 levels, thereby regulating glucose uptake and inhibiting aerobic glycolysis
Glycolysis↓,
Akt↓, In LNCaP cells, DHA reduced Akt/mTOR and HIF-1α activity, leading to decreased expression of GLUT1, HK2, PKM2, and LDH and subsequent inhibition of aerobic glycolysis
mTOR↓,
Hif1a↓,
HK2↓,
LDH↓,
NF-kB↓, DHA was also found to inhibit the NF-κB signaling pathway to prevent GLUT1 translocation to the plasma membrane, thereby inhibiting the progression of non-small-cell lung cancer (NSCLC) cells via targeting glucose metabolism

957- ART/DHA,    Artemisinin inhibits the development of esophageal cancer by targeting HIF-1α to reduce glycolysis levels
- in-vitro, ESCC, KYSE150 - in-vitro, ESCC, KYSE170
TumCP↓,
TumMeta↓,
Glycolysis↓,
N-cadherin↓,
PKM2↓,
Hif1a↓,

985- ART/DHA,    Artemisinin suppresses aerobic glycolysis in thyroid cancer cells by downregulating HIF-1a, which is increased by the XIST/miR-93/HIF-1a pathway
- in-vitro, Thyroid, TPC-1 - Human, NA, NA
XIST↓, HIF-1a is highly expressed in TC tissues and is positively correlated with the level of XIST in the serum of patients with TC.
Hif1a↓,
Glycolysis↓,
TumCCA↑, inhibited the cell cycle, and G1 phase cells increased by 17%
TumMeta↓, 51%

1180- Ash,    Withaferin A Inhibits Liver Cancer Tumorigenesis by Suppressing Aerobic Glycolysis through the p53/IDH1/HIF-1α Signaling Axis
- in-vitro, Liver, HepG2
IDH1↑, IDH1 expression was downregulated in human liver cancer cells compared to normal liver cells
Glycolysis↓, decreased levels of several glycolytic enzymes
P53↑,
Hif1a↓,

1176- Ash,    Metabolic Alterations in Mammary Cancer Prevention by Withaferin A in a Clinically Relevant Mouse Model
- in-vivo, NA, NA
TumVol↓, lower by 94%
Apoptosis↑,
Glycolysis↓, reduced levels of glycolysis intermediates.
PKM2↓,
PGK1↓,
ALDOAiso2↓,

2388- Ash,    Withaferin A decreases glycolytic reprogramming in breast cancer
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468 - in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-453
GlucoseCon↓, WA decreases the glucose uptake, lactate production and ATP generation by inhibiting the expression of key glycolytic enzymes i.e., GLUT1, HK2 and PKM2.
lactateProd↓,
ATP↓,
Glycolysis↓,
GLUT1↓,
HK2↓,
PKM2↓,
cMyc↓, WA decreases the protein expression of key glycolytic enzymes via downregulation of c-myc expression
Warburg↓, WA decreases protein expression of key glycolytic enzymes and Warburg effect via c-myc inhibition
cMyc↓,

3156- Ash,    Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug
- Review, Var, NA
MAPK↑, Figure 3
p38↑,
BAX↑,
BIM↑,
CHOP↑,
ROS↑,
DR5↑,
Apoptosis↑,
Ferroptosis↑,
GPx4↓,
BioAv↝, WA has a rapid oral absorption and reaches to peak plasma concentration of around 16.69 ± 4.02 ng/ml within 10 min after oral administration of Withania somnifera aqueous extract at dose of 1000 mg/kg, which is equivalent to 0.458 mg/kg of WA
HSP90↓, table 1 10uM) were found to inhibit the chaperone activity of HSP90
RET↓,
E6↓,
E7↓,
Akt↓,
cMET↓,
Glycolysis↓, by suppressing the glycolysis and tricarboxylic (TCA) cycle
TCA↓,
NOTCH1↓,
STAT3↓,
AP-1↓,
PI3K↓,
eIF2α↓,
HO-1↑,
TumCCA↑, WA (1--3 uM) have been reported to inhibit cell proliferation by inducing G2 and M phase cycle arrest inovarian, breast, prostate, gastric and myelodysplastic/leukemic cancer cells and osteosarcoma
CDK1↓, WA is able to decrease the cyclin-dependent kinase 1 (Cdk1) activity and prevent Cdk1/cyclin B1 complex formation, which are key steps in cell cycle progression
*hepatoP↑, A treatment (40 mg/kg) reduces acetaminophen-induced liver injury (AILI) in mouse models and decreases H 2O 2-induced glutathione (GSH) depletion and necrosis in hepatocyte
*GSH↑,
*NRF2↑, WA triggers an anti-oxidant response after acetaminophen overdose by enhancing hepatic transcription of the nuclear factor erythroid 2–related factor 2 (NRF2)-responsive gene
Wnt↓, indirectly inhibit Wnt
EMT↓, WA can also block tumor metastasis through reduced expression of epithelial mesenchymal transition (EMT) markers.
uPA↓, WA (700 nM) exert anti-meta-static activities in breast cancer cells through inhibition of the urokinase-type plasminogen activator (uPA) protease
CSCs↓, s WA (125-500 nM) suppress tumor sphere formation indicating that the self-renewal of CSC is abolished
Nanog↓, loss of these CSC-specific characteristics is reflected in the loss of typical stem cell markers such as ALDH1A, Nanog, Sox2, CD44 and CD24
SOX2↓,
CD44↓,
lactateProd↓, drop in lactate levels compared to control mice.
Iron↑, Furthermore, we found that WA elevates the levels of intracellular labile ferrous iron (Fe +2 ) through excessive activation of heme oxygenase-1 (HMOX1), which independently causes accumulation of toxic lipid radicals and ensuing ferroptosis
NF-kB↓, nhibition of NF-kB kinase signaling pathway

3162- Ash,    Molecular insights into cancer therapeutic effects of the dietary medicinal phytochemical withaferin A
- Review, Var, NA
lipid-P↓, Oral cancer 20 mg/Kg ↓Lipid peroxidation : ↑SOD, glutathione peroxidase, p53, Bcl-2
SOD↑,
GPx↑,
P53↑,
Bcl-2↑,
E6↓, Cervival cancer 8mg/Kg ↓E6, E7: ↑p53, pRb, Cyclin B1, P34 Cdc2, p21, PCNA
E7↓,
pRB↑,
CycB/CCNB1↑,
CDC2↑,
P21↑,
PCNA↓,
ALDH1A1↓, Mammary cancer 0-1 mg/mouse (5-10) ↓Mammosphere number, ALDH1 activity. Vimentin, glycolysis
Vim↓,
Glycolysis↓,
cMyc↓, Mesotheliome cancer 5 mg/Kg ↓Proteasomal chymotrypsin, C-Myc : ↑ Bax, CARP-1
BAX↑,
NF-kB↓,
Casp3↑, caspase-3 activation
CHOP↑, WA is found to increase activation of Elk1 and CHOP (CCAAT-enhancer-binding protein homologous protein) by RSK, as well as up-regulation of DR5 by selectively suppressing pathway ERK
DR5↑,
ERK↓,
Wnt↓, WA inhibits Wnt/β-catenin pathway via suppression of AKT signalling, which inhibits cancer cell motility and sensitises for cell death
β-catenin/ZEB1↓,
Akt↓,
HSP90↓, WA-dependent inhibition of heat shock protein (HSP) chaperone functions. WA inhibits the activity of HSP90-mediated function

996- Ba,  Tam,    Baicalein resensitizes tamoxifen‐resistant breast cancer cells by reducing aerobic glycolysis and reversing mitochondrial dysfunction via inhibition of hypoxia‐inducible factor‐1α
Hif1a↓,
Glycolysis↓,
GlucoseCon↓,
lactateProd↓,
lact/pyru↓,
ROS↑, baicalein significantly increased mitochondrial ROS.
Apoptosis↑,

2620- Ba,    Natural compounds targeting glycolysis as promising therapeutics for gastric cancer: A review
- Review, GC, NA
Hif1a↓, Baicalein reduces the levels of HIF-1α in AGS gastric cancer cells in a dose-dependent manner (10, 20, and 40 µM)
HK2↓, down-regulates the levels of HK2, LDHA, and PDK1
LDHA↓,
PDK1↓,
p‑Akt↓, inhibits Akt phosphorylation under hypoxic conditions
PTEN↑, promotes the expression of PTEN protein
GlucoseCon↓, gradually restores glucose uptake and lactic acid production in hypoxic AGS cells to those observed under normoxic conditions
lactateProd↓,
Glycolysis↓, Baicalein and other compounds could directly regulate glycolysis-related enzymes

2617- Ba,    Potential of baicalein in the prevention and treatment of cancer: A scientometric analyses based review
- Review, Var, NA
Ca+2↑, MDA-MB-231 ↑Ca2+
MMP2↓, MDA-MB-231 ↓MMP-2/9
MMP9↓,
Vim↓, ↓Vimentin, ↓SNAIL, ↑E-cadherin, ↓Wnt1, ↓β-catenin
Snail↓,
E-cadherin↑,
Wnt↓,
β-catenin/ZEB1↓,
p‑Akt↓, MCF-7 ↓p-Akt, ↓p-mTOR, ↓NF-κB
p‑mTOR↓,
NF-kB↓,
i-ROS↑, MCF-7 ↑Intracellular ROS, ↓Bcl-2, ↑Bax, ↑cytochrome c, ↑caspase-3/9
Bcl-2↓,
BAX↑,
Cyt‑c↑,
Casp3↑,
Casp9↑,
STAT3↓, 4T1, MDA-MB-231 ↓STAT3, ↓ IL-6
IL6↓,
MMP2↓, HeLa ↓MMP-2, ↓MMP-9
MMP9↓,
NOTCH↓, ↓Notch 1
PPARγ↓, ↓PPARγ
p‑NRF2↓, HCT-116 ↓p-Nrf2
HK2↓, ↓HK2, ↓LDH-A, ↓PDK1, ↓glycolysis, PTEN/Akt/HIF-1α regulation
LDHA↓,
PDK1↓,
Glycolysis↓,
PTEN↑, Furthermore, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-alpha ( HIF-1a) expression in AGS cells.
Akt↓,
Hif1a↓,
MMP↓, SGC-7901 ↓ΔΨm
VEGF↓, ↓VEGF, ↓VEGFR2
VEGFR2↓,
TOP2↓, ↓Topoisomerase II
uPA↓, ↓u-PA, ↓TIMP1, ↓TIMP2
TIMP1↓,
TIMP2↓,
cMyc↓, ↓β-catenin, ↓c-Myc, ↓cyclin D1, ↓Axin-2
TrxR↓, EL4 ↓Thioredoxin reductase, ↑ASK1,
ASK1↑,
Vim↓, ↓vimentin
ZO-1↑, ↑ZO-1
E-cadherin↑, ↑E-cadherin
SOX2↓, PANC-1, BxPC-3, SW1990 ↓Sox-2, ↓Oct-4, ↓SHH, ↓SMO, ↓Gli-2
OCT4↓,
Shh↓,
Smo↓,
Gli1↓,
N-cadherin↓, ↓N-cadherin
XIAP↓, ↓XIAP

2616- Ba,    The Role of HK2 in Tumorigenesis and Development: Potential for Targeted Therapy with Natural Products
- Review, Var, NA
Glycolysis↓, Related experiments have found that baicalein, the aglycone of baicalein inhibited hypoxia-enhanced glycolytic flux in AGS cells
HK2↓, and reduced the expression of key glycolytic-related enzymes such as HK2, lactate dehydrogenase A (LDH-A) and pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK1)
LDHA↓,
PDK1↓,
PTEN↑, Baicalein can also inhibit hypoxia-induced AKT phosphorylation by enhancing PTEN accumulation

2615- Ba,    The Multifaceted Role of Baicalein in Cancer Management through Modulation of Cell Signalling Pathways
- Review, Var, NA
*AntiCan↓, Baicalein is known to display anticancer activity through the inhibition of inflammation and cell proliferation
*Inflam↓,
TumCP↓,
NF-kB↓, baicalein decreased the activation of nuclear factor-κB (NF-κB)
PPARγ↑, anti-inflammatory effects of baicalein might be initiated via PPARγ activation.
TumCCA↑, baicalein inhibited cell cycle progression and cell growth, and promoted apoptosis of cancer cells
JAK2↓, inactivation of the signaling pathway JAK2/STAT3 [63]
STAT3↓,
TumCMig↓, baicalein suppressed migration as well as invasion through decreasing the aerobic glycolysis and expression of MMP-2/9 proteins.
Glycolysis↓,
MMP2↓,
MMP9↓,
selectivity↑, Furthermore, baicalein and baicalin had less inhibitory effects on normal ovarian cells’ viability.
VEGF↓, baicalein is more effective in inhibiting the expressions of VEGF, HIF-1α, cMyc, and NFκB
Hif1a↓,
cMyc↓,
ChemoSen↑, baicalein enhanced the cisplatin sensitivity of SGC-7901/DDP gastric cancer cells by inducing autophagy and apoptosis through the Akt/mTOR and Keap 1/Nrf2 pathways
ROS↑, oral squamous cell carcinoma Cal27 cells. Significantly, it was noticed that baicalein activated reactive oxygen species (ROS) generation in Cal27 cells
p‑mTOR↓, results suggest that p-mTOR, p-Akt, p-IκB, and NF-κB protein expressions were decreased
PTEN↑, Baicalein upregulated PTEN expression, downregulated miR-424-3p, and downregulated PI3K and p-Akt.

2289- Ba,  Rad,    Baicalein Inhibits the Progression and Promotes Radiosensitivity of Esophageal Squamous Cell Carcinoma by Targeting HIF-1A
- in-vitro, ESCC, KYSE150
TumCP↓, Radiation combined with baicalein could significantly inhibit the proliferation and migration of esophageal cancer cells compared with that of 6 Gy rays alone
TumCMig↓,
Glycolysis↓, 20μM baicalein reduced glycolysis in KYSE150 cells
cycD1/CCND1↓,
CDK4↓,
ECAR↓, Baicalein reduces ECAR and glycoPER
TumCCA↑, baicalein arrested cells in the G1 phase of the cell cycle
HK1↓, HK1 (4QS9),13 ALDH2, GPI and ALDOA are the key enzymes in the process of glycolysis.
ALDH↓,
ALDOA↓,
PKM2↓, protein levels of HIF-1A and PKM2 decreased significantly after baicalein treatment.
Hif1a↓,

2293- Ba,    Baicalein suppresses inflammation and attenuates acute lung injury by inhibiting glycolysis via HIF‑1α signaling
- in-vitro, Nor, MH-S - in-vivo, NA, NA
*Hif1a↓, baicalein could inhibit HIF‑1α signaling, thus suppressing glycolysis, and improving inflammatory responses
*Glycolysis↓, Baicalein inhibits glycolysis in LPS-induced macrophages and in the lung tissues of mice with LPS-induced ALI
*Inflam↓, Baicalein inhibits the inflammatory response in LPS-induced macrophages and mice with LPS-induced ALI
*HK2↓, baicalein could inhibit the expression of key glycolysis-related enzymes (HK2, PFK1 and PKM2) in the lungs of mice with LPS-induced ALI and in LPS-induced macrophages
*PFK1↓,
*PKM2↓,

2295- Ba,  5-FU,    Baicalein reverses hypoxia-induced 5-FU resistance in gastric cancer AGS cells through suppression of glycolysis and the PTEN/Akt/HIF-1α signaling pathway
- in-vitro, GC, AGS
ChemoSen↑, baicalein increased the sensitivity of AGS cells to 5-FU treatment under hypoxia
HK2↓, hypoxia-enhanced glycolytic flux and expression of several critical glycolysis-associated enzymes (HK2, LDH-A and PDK1) in the AGS cells were suppressed by baicalein
LDHA↓,
PDK1↓,
Akt↓, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-1α (HIF-1α) expression in AGS cells
PTEN↑,
Hif1a↓,
Glycolysis↓, results together suggest that inhibition of glycolysis via regulation of the PTEN/Akt/HIF-1α signaling pathway may be one of the mechanisms whereby baicalein reverses 5-FU resistance in cancer cells under hypoxia.
ROS↑, Taniguchi et al found that baicalein overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in cancer cells through DR5 upregulation mediated by ROS induction and CHOP/GADD153 activation
CHOP↑,

2297- Ba,    Significance of flavonoids targeting PI3K/Akt/HIF-1α signaling pathway in therapy-resistant cancer cells – A potential contribution to the predictive, preventive, and personalized medicine
- Review, Var, NA
Glycolysis↓, baicalein to re-sensitize tamoxifen-resistant breast cancer cells in vitro and in vivo through the attenuation of aerobic glycolysis and reversion of mitochondrial dysfunction via reduced HIF-1α expression and transcriptional activity
Hif1a↓, inhibition of HIF-1α and PKM2 by baicalein resulted in the glycolysis suppression
PKM2↓, baicalein enhanced radio-sensitivity and inhibited the progression of esophageal squamous cell carcinoma by affecting HIF-1α and PKM2.
RadioS↑,

2298- Ba,    Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
- Review, Var, NA
TumCG↓, Baicalein significantly reduced intracerebral tumor growth and proliferation and promoted apoptosis and cell cycle arrest in orthotopic U87 gliomas in mice
TumCP↓,
Hif1a↓, suppression of HIF-1α by baicalein contributed to its reduction of cell viability in ovarian cancer (OVCAR-3 and CP-70) cell lines. 20-μM and 40-μM.
VEGF↓, Suppression of HIF-1α/VEGF pathway
ChemoSen↑, Moreover, baicalein increased the sensitivity of gastric cancer cells (AGS) to 5-fluorouracil (5-FU) under hypoxic conditions
Glycolysis↓, baicalein suppressed the expression of glycolysis-associated enzymes including HKII, PDK1, and LDHA via inhibition of Akt-phosphorylation, which led to HIF-1α suppression
HK2↓,
PDK1↓,
LDHA↓,
p‑Akt↓,
PTEN↑, Furthermore, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-alpha ( HIF-1a) expression in AGS cells. (orginal paper)

2391- Ba,    Scutellaria baicalensis and its flavonoids in the treatment of digestive system tumors
- Review, GC, NA
Hif1a↓, pretreatment of baicalein increased the sensitivity of tumor cells to 6Gy ray by down-regulating HIF-1A and PKM2, the key regulators of glycolysis.
PKM2↓,
RadioS↑,
Glycolysis↓,
PAK↓, baicalein dose-dependently inhibited the growth of EC in mice with a decrease in PAK4 protein

2389- BA,    Baicalin alleviates lipid accumulation in adipocytes via inducing metabolic reprogramming and targeting Adenosine A1 receptor
- in-vitro, Obesity, 3T3
*ECAR↑, Baicalin promoted metabolic reprogramming in 3T3-L1 preadipocytes, characterized by increased ECAR and decreased OCR
*OCR↓,
*p‑AMPK↑, baicalin significantly altered cellular respiration by reducing mitochondrial oxygen consumption while enhancing glycolytic flux, accompanied by increased phosphorylation of AMPK and ACC, suggesting an adaptation to altered energy availability.
*p‑ACC↑,
*Glycolysis↑, significant enrichment in metabolic pathways such as glycolysis, gluconeogenesis, and lipid metabolism.
*lipidDe↓, inhibited the maturation of sterol regulatory element binding protein 1 (SREBP1) and finally alleviated lipid deposition.
*SREBP1↓,
*FAO↑, baicalin induces metabolic reprogramming of adipocytes by inhibiting glucose aerobic metabolism while enhancing anaerobic glycolysis and FAO.
*HK2↑, baicalin upregulated glycolytic enzymes, such as HK1, HK2, PKM2, and LDHA, while downregulating pyruvate dehydrogenase,
*PKM2↑,
*LDHA↑,
*PDKs↓,
*ACC↓, leading to decreased acetyl-CoA production and enhanced fatty acid β-oxidation.

932- BBR,    The short-term effects of berberine in the liver: Narrow margins between benefits and toxicity
- in-vivo, Nor, NA
*glucoNG↓, These results can be regarded as evidence that the direct inhibitory effects of berberine on gluconeogenesis
*Glycolysis↑,
*NH3↑, inhibited ammonia detoxification
*NADPH/NADP+↑,
*ATP↓,
*toxicity↑, narrow margin between the expected benefits and toxicity

2335- BBR,    Chemoproteomics reveals berberine directly binds to PKM2 to inhibit the progression of colorectal cancer
- in-vitro, CRC, HT29 - in-vitro, CRC, HCT116 - in-vivo, NA, NA
PKM2↓, berberine is directly bound to pyruvate kinase isozyme type M2 (PKM2) in colorectal cancer cells. Berberine inhibited PKM2 activity
Glycolysis↓, berberine was shown to inhibit the reprogramming of glucose metabolism and the phosphorylation of STAT3, down regulate the expression of Bcl-2 and Cyclin D1 genes
p‑STAT3↓,
Bcl-2↓,
cycD1/CCND1↓,
TumCG↓, n vivo experiments showed that tumor growth was inhibited in HT29 cell-bearing mice injected intraperitoneally with berberine (5 or 10 mg/kg body weight)
Ki-67↓, Berberine inhibited the proliferation index (Ki67 expression)
lactateProd↓, Berberine inhibited lactate production, glucose uptake, pyruvate production, and PKM2 activity in HWT tumor tissues, but no apparent effects were observed in both F244A mutant cells and I199S mutant tumor tissues
glucose↓,

2707- BBR,    Berberine exerts its antineoplastic effects by reversing the Warburg effect via downregulation of the Akt/mTOR/GLUT1 signaling pathway
- in-vitro, Liver, HepG2 - in-vitro, BC, MCF-7
GLUT1↓, BBR downregulated the protein expression levels of GLUT1, maintained the cytoplasmic internalization of GLUT1
Akt↓, and suppressed the Akt/mTOR signaling pathway in both HepG2 and MCF7 cell lines
mTOR↓,
ATP↓, BBR-induced decrease in ATP synthesis, glucose uptake, GLUT1 expression and cell proliferation
GlucoseCon↓,
TumCP↓,
Warburg↓, antineoplastic effect of BBR may involve the reversal of the Warburg effect
selectivity↑, The results demonstrated that the colony-forming capacity was slightly inhibited in Hs 578Bst normal breast cells following BBR treatment, but significantly inhibited in both cancer cell lines.
TumCCA↑, BBR effectively induced cell cycle arrest at the G2M phase
Glycolysis↓, Notably, our preliminary experiments identified that BBR strongly decreased the glucose uptake ability of HepG2 and MCF7 cell lines, therefore, it was hypothesized that BBR may interfere with tumor progression by inhibiting glycolysis.

2708- BBR,    Berberine decelerates glucose metabolism via suppression of mTOR‑dependent HIF‑1α protein synthesis in colon cancer cells
- in-vitro, CRC, HCT116
TumCG↓, we revealed that berberine, which suppressed the growth of colon cancer cell lines HCT116 and KM12C, greatly inhibited the glucose uptake and the transcription of glucose metabolic genes, GLUT1, LDHA and HK2 in these two cell lines
GlucoseCon↓,
GLUT1↓,
LDHA↓, berberine inhibited the mRNA levels of LDHA and HK2 in a concentration-dependent manner
HK2↓,
Hif1a↓, protein expression but not mRNA transcription of HIF‑1α, a well‑known transcription factor critical for dysregulated cancer cell glucose metabolism, was dramatically inhibited in berberine‑treated colon cancer cell lines
mTOR↓, mTOR signaling previously reported to regulate HIF‑1α protein synthesis was further found to be suppressed by berberine.
Glycolysis↓, berberine inhibits overactive glucose metabolism of colon cancer cells via suppressing mTOR‑depended HIF‑1α protein synthesis

2709- BBR,    Berberine inhibits the glycolysis and proliferation of hepatocellular carcinoma cells by down-regulating HIF-1α
- in-vitro, HCC, HepG2
TumCP↓, After exposure to 100 μmol/L BBR, the proliferation, migration and invasion of HepG2 cells were reduced, along with apoptosis was increased, while the levels of glycolysis-related proteins were decreased
TumCMig↓,
TumCI↓,
Apoptosis↑,
Glycolysis↓, BBR inhibits proliferation and glycolysis of HCC cells in vivo
Hif1a↓, BBR can down-regulate HIF-1α in the hypoxic microenvironment, and hinder the proliferation and metastasis of breast cancer cell
GLUT1↓, treatment with 100μmol/L BBR for 48 h, the levels of GLUT1, HK2, PKM2, and LDHA mRNA were markedly reduced in HepG2 cells
HK2↓,
PKM2↓,
LDHA↓,

2710- BBR,    Berberine inhibits the Warburg effect through TET3/miR-145/HK2 pathways in ovarian cancer cells
- in-vitro, Ovarian, SKOV3
Warburg↓, berberine inhibited the Warburg effect by up-regulating miR-145, miR-145 targeted HK2 directly.
miR-145↑,
HK2↓, westernblot suggested that berberine could significantly down regulate the expression of HK2
TET3↑, Berberine increased the expression of miR-145 by promoting the expression of TET3 and reducing the methylation level of the promoter region of miR-145 precursor gene.
Glycolysis↓, Furthermore, the effect of berberine on glycolysis related enzymes was detected, the results of qRT-PCR and westernblot suggested that berberine could significantly down regulate the expression of HK2
PKM2↓, Western blot results showed down-expression of miR-145 reversed berberine's inhibition of HK2 expression. PKM2, pyruvate kinase M2; HK2, Hexokinase2; GLUT1, glucose transporter 1; LDH, lactate dehydrogenase; PFK2, phosphofructokinase 2; PDK1,
GLUT1↓,
LDH↓,
PFK2↓,
PDK1↓,

2686- BBR,    Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs
- Review, Nor, NA
Inflam↓, BBR has documented to have anti-diabetic, anti-inflammatory and anti-microbial (both anti-bacterial and anti-fungal) properties.
IL6↓, BBRs can inhibit IL-6, TNF-alpha, monocyte chemo-attractant protein 1 (MCP1) and COX-2 production and expression.
MCP1↓,
COX2↓,
PGE2↓, BBRs can also effect prostaglandin E2 (PGE2)
MMP2↓, and decrease the expression of key genes involved in metastasis including: MMP2 and MMP9.
MMP9↓,
DNAdam↑, BBR induces double strand DNA breaks and has similar effects as ionizing radiation
eff↝, In some cell types, this response has been reported to be TP53-dependent
Telomerase↓, This positively-charged nitrogen may result in the strong complex formations between BBR and nucleic acids and induce telomerase inhibition and topoisomerase poisoning
Bcl-2↓, BBR have been shown to suppress BCL-2 and expression of other genes by interacting with the TATA-binding protein and the TATA-box in certain gene promoter regions
AMPK↑, BBR has been shown in some studies to localize to the mitochondria and inhibit the electron transport chain and activate AMPK.
ROS↑, targeting the activity of mTOR/S6 and the generation of ROS
MMP↓, BBR has been shown to decrease mitochondrial membrane potential and intracellular ATP levels.
ATP↓,
p‑mTORC1↓, BBR induces AMPK activation and inhibits mTORC1 phosphorylation by suppressing phosphorylation of S6K at Thr 389 and S6 at Ser 240/244
p‑S6K↓,
ERK↓, BBR also suppresses ERK activation in MIA-PaCa-2 cells in response to fetal bovine serum, insulin or neurotensin stimulation
PI3K↓, Activation of AMPK is associated with inhibition of the PI3K/PTEN/Akt/mTORC1 and Raf/MEK/ERK pathways which are associated with cellular proliferation.
PTEN↑, RES was determined to upregulate phosphatase and tensin homolog (PTEN) expression and decrease the expression of activated Akt. In HCT116 cells, PTEN inhibits Akt signaling and proliferation.
Akt↓,
Raf↓,
MEK↓,
Dose↓, The effects of low doses of BBR (300 nM) on MIA-PaCa-2 cells were determined to be dependent on AMPK as knockdown of the alpha1 and alpha2 catalytic subunits of AMPK prevented the inhibitory effects of BBR on mTORC1 and ERK activities and DNA synthes
Dose↑, In contrast, higher doses of BBR inhibited mTORC1 and ERK activities and DNA synthesis by AMPK-independent mechanisms [223,224].
selectivity↑, BBR has been shown to have minimal effects on “normal cells” but has anti-proliferative effects on cancer cells (e.g., breast, liver, CRC cells) [225–227].
TumCCA↑, BBR induces G1 phase arrest in pancreatic cancer cells, while other drugs such as gemcitabine induce S-phase arrest
eff↑, BBR was determined to enhance the effects of epirubicin (EPI) on T24 bladder cancer cells
EGFR↓, In some glioblastoma cells, BBR has been shown to inhibit EGFR signaling by suppression of the Raf/MEK/ERK pathway but not AKT signaling
Glycolysis↓, accompanied by impaired glycolytic capacity.
Dose?, The IC50 for BBR was determined to be 134 micrograms/ml.
p27↑, Increased p27Kip1 and decreased CDK2, CDK4, Cyclin D and Cyclin E were observed.
CDK2↓,
CDK4↓,
cycD1/CCND1↓,
cycE/CCNE↓,
Bax:Bcl2↑, Increased BAX/BCL2 ratio was observed.
Casp3↑, The mitochondrial membrane potential was disrupted and activated caspase 3 and caspases 9 were observed
Casp9↑,
VEGFR2↓, BBR treatment decreased VEGFR, Akt and ERK1,2 activation and the expression of MMP2 and MMP9 [235].
ChemoSen↑, BBR has been shown to increase the anti-tumor effects of tamoxifen (TAM) in both drug-sensitive MCF-7 and drug-resistant MCF-7/TAM cells.
eff↑, The combination of BBR and CUR has been shown to be effective in suppressing the growth of certain breast cancer cell lines.
eff↑, BBR has been shown to synergize with the HSP-90 inhibitor NVP-AUY922 in inducing death of human CRC.
PGE2↓, BBR inhibits COX2 and PEG2 in CRC.
JAK2↓, BBR prevented the invasion and metastasis of CRC cells via inhibiting the COX2/PGE2 and JAK2/STAT3 signaling pathways.
STAT3↓,
CXCR4↓, BBR has been observed to inhibit the expression of the chemokine receptors (CXCR4 and CCR7) at the mRNA level in esophageal cancer cells.
CCR7↓,
uPA↓, BBR has also been shown to induce plasminogen activator inhibitor-1 (PAI-1) and suppress uPA in HCC cells which suppressed their invasiveness and motility.
CSCs↓, BBR has been shown to inhibit stemness, EMT and induce neuronal differentiation in neuroblastoma cells. BBR inhibited the expression of many genes associated with neuronal differentiation
EMT↓,
Diff↓,
CD133↓, BBR also suppressed the expression of many genes associated with cancer stemness such as beta-catenin, CD133, NESTIN, N-MYC, NOTCH and SOX2
Nestin↓,
n-MYC↓,
NOTCH↓,
SOX2↓,
Hif1a↓, BBR inhibited HIF-1alpha and VEGF expression in prostate cancer cells and increased their radio-sensitivity in in vitro as well as in animal studies [290].
VEGF↓,
RadioS↑,

943- BetA,    Betulinic acid suppresses breast cancer aerobic glycolysis via caveolin-1/NF-κB/c-Myc pathway
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
Glycolysis↓,
lactateProd↓,
GlucoseCon↓,
ECAR↓,
cMyc↓,
LDHA↓,
p‑PDK1↓,
PDK1↓,
Cav1↑, Cav-1) as one of key targets of BA in suppressing aerobic glycolysis, as BA administration resulted in Cav-1 upregulation
*Glycolysis↑, BA could lead to increased glycolysis in mouse embryonic fibroblasts by activating LKB1/AMPK pathway, whereas we found that BA inhibited aerobic glycolysis in breast cancer cells by modulating Cav-1/NF-κB/c-Myc signaling
selectivity↑,
OCR↓, OCR parameters including the basal respiration, maximal respiration and spare respiratory capacity were also simultaneously inhibited
OXPHOS↓, implying that the activity of mitochondrial oxidative phosphorylation (OXPHOS) chain was also suppressed by BA

2729- BetA,    Betulinic acid in the treatment of tumour diseases: Application and research progress
- Review, Var, NA
ChemoSen↑, Betulinic acid can increase the sensitivity of cancer cells to other chemotherapy drugs
mt-ROS↑, BA has antitumour activity, and its mechanisms of action mainly include the induction of mitochondrial oxidative stress
STAT3↓, inhibition of signal transducer and activator of transcription 3 and nuclear factor-κB signalling pathways.
NF-kB↓,
selectivity↑, A main advantage of BA and its derivatives is that they are cytotoxic to different human tumour cells, while cytotoxicity is much lower in normal cells.
*toxicity↓, It can kill cancer cells but has no obvious effect on normal cells and is also nontoxic to other organs in xenograft mice at a dose of 500 mg/kg
eff↑, BA combined with chemotherapy drugs, such as platinum and mithramycin A, can induce apoptosis in tumour cells
GRP78/BiP↑, In animal xenograft tumour models, BA enhanced the expression of glucose-regulated protein 78 (GRP78)
MMP2↓, reduced the levels of matrix metalloproteinases (MMPs), such as MMP-2 and MMP-9, in lung metastatic lesions of breast cancer, indicating that BA can reduce the invasiveness of breast cancer in vivo and block epithelial mesenchymal transformation (EMT
P90RSK↓,
TumCI↓,
EMT↓,
MALAT1↓, MALAT1, a lncRNA, was downregulated in hepatocellular carcinoma (HCC) cells treated with BA in vivo,
Glycolysis↓, Suppressing aerobic glycolysis of cancer cells by GRP78/β-Catenin/c-Myc signalling pathways
AMPK↑, activating AMPK signaling pathway
Sp1/3/4↓, inhibiting Sp1. BA at 20 mg/kg/d, the tumour volume and weight were significantly reduced, and the expression levels of Sp1, Sp3, and Sp4 in tumour tissues were lower than those in control mouse tissues
Hif1a↓, Suppressing the hypoxia-induced accumulation of HIF-1α and expression of HIF target genes
angioG↓, PC3: Having anti-angiogenesis effect
NF-kB↑, LNCaP, DU145 — Inducing apoptosis and NF-κB pathway
NF-kB↓, U266 — Inhibiting NF-κB pathway.
MMP↓, BA produces ROS and reduces mitochondrial membrane potential; the mitochondrial permeability transition pore of the mitochondrial membrane plays an important role in apoptosis signal transduction.
Cyt‑c↑, Mitochondria release cytochrome C and increase the levels of Caspase-9 and Caspase-3, inducing cell apoptosis.
Casp9↑,
Casp3↑,
RadioS↑, BA could be a promising drug for increasing radiosensitization in oral squamous cell carcinoma radiotherapy.
PERK↑, BA treatment increased the activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/C/EBP homologous protein (CHOP) apoptosis pathway and decreased the expression of Sp1.
CHOP↑,
*toxicity↓, BA at a concentration of 50 μg/ml did not inhibit the growth of normal peripheral blood lymphocytes, indicating that the toxicity of BA was at least 1000 times less than that of doxorubicin

2738- BetA,    Betulinic Acid Suppresses Breast Cancer Metastasis by Targeting GRP78-Mediated Glycolysis and ER Stress Apoptotic Pathway
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, BT549 - in-vivo, NA, NA
TumCI↓, BA inhibited invasion and migration of highly aggressive breast cancer cells.
TumCMig↓,
Glycolysis↓, Moreover, BA could suppress aerobic glycolysis of breast cancer cells presenting as a reduction of lactate production, quiescent energy phenotype transition, and downregulation of aerobic glycolysis-related proteins.
lactateProd↓, lactate production in both MDA-MB-231 and BT-549 cells was significantly reduced following BA administration
GRP78/BiP↑, (GRP78) was also identified as the molecular target of BA in inhibiting aerobic glycolysis. BA treatment led to GRP78 overexpression, and GRP78 knockdown abrogated the inhibitory effect of BA on glycolysis.
ER Stress↑, Further studies demonstrated that overexpressed GRP78 activated the endoplasmic reticulum (ER) stress sensor PERK.
PERK↑,
p‑eIF2α↑, Subsequent phosphorylation of eIF2α led to the inhibition of β-catenin expression, which resulted in the inhibition of c-Myc-mediated glycolysis.
β-catenin/ZEB1↓,
cMyc↓, These findings suggested that BA inhibited the β-catenin/c-Myc pathway by interrupting the binding between GRP78 and PERK and ultimately suppressed the glycolysis of breast cancer cells.
ROS↑, (i) the induction of cancer cell apoptosis via the mitochondrial pathway induced by the release of soluble factors or generation of reactive oxygen species (ROS)
angioG↓, (ii) the inhibition of angiogenesis [24];
Sp1/3/4↓, (iii) the degradation of transcription factor specificity protein 1 (Sp1)
DNAdam↑, (iv) the induction of DNA damage by suppressing topoisomerase I
TOP1↓,
TumMeta↓, BA Inhibits Metastasis of Highly Aggressive Breast Cancer Cells
MMP2↓, BA significantly decreased the expression of MMP-2 and MMP-9 secreted by breast cancer cells
MMP9↓,
N-cadherin↓, BA downregulated the levels of N-cadherin and vimentin as the mesenchymal markers, while increased E-cadherin which is an epithelial marker (Figure 2(c)), validating the EMT inhibition effects of BA in breast cancer cells.
Vim↓,
E-cadherin↑,
EMT↓,
LDHA↓, the levels of glycolytic enzymes, including LDHA and p-PDK1/PDK1, were all decreased in a dose-dependent manner by BA
p‑PDK1↓,
PDK1↓,
ECAR↓, extracellular acidification rate (ECAR), which reflects the glycolysis activity, was retarded following BA administration.
OCR↓, oxygen consumption rate (OCR), which is a marker of mitochondrial respiration, was also decreased simultaneously
Hif1a↓, BA could reduce prostate cancer angiogenesis via inhibiting the HIF-1α/stat3 pathway [39]
STAT3↓,

2739- BetA,    Glycolytic Switch in Response to Betulinic Acid in Non-Cancer Cells
- in-vitro, Nor, HUVECs - in-vitro, Nor, MEF
*Glycolysis↑, BA elevates the rates of cellular glucose uptake and aerobic glycolysis in mouse embryonic fibroblasts with concomitant reduction of glucose oxidation.
*GlucoseCon↑, BA increases cellular glucose uptake
*Apoptosis↓, Without eliciting signs of obvious cell death BA leads to compromised mitochondrial function, increased expression of mitochondrial uncoupling proteins (UCP) 1 and 2, and liver kinase B1 (LKB1)-dependent activation AMP-activated protein kinase.
*UCP1↓,
*AMPK↑, AMPK activation accounts for the increased glucose uptake and glycolysis which in turn are indispensable for cell viability upon BA treatment.
GLUT1↑, The expression of glucose transporter GLUT1 was elevated upon BA treatment for 16 h
mt-ROS↑, We observed increased production of mitochondrial ROS (Fig. 4A) and elevated expression of uncoupling proteins UCP1 and UCP2 in BA-treated MEF

2740- BetA,    Effects and mechanisms of fatty acid metabolism-mediated glycolysis regulated by betulinic acid-loaded nanoliposomes in colorectal cancer
- in-vitro, CRC, HCT116
TumCP↓, BA-NLs significantly suppressed the proliferation and glucose uptake of CRC cells by regulating potential glycolysis and fatty acid metabolism targets and pathways, which forms the basis of the anti-CRC function of BA-NLs.
Glycolysis↓,
HK2↓, HK2, PFK-1, PEP and PK isoenzyme M2 (PKM2) in glycolysis, and of ACSL1, CPT1a and PEP in fatty acid metabolism, were blocked by BA-NLs, which play key roles in the inhibition of glycolysis and fatty acid-mediated production of pyruvate and lactate.
PFK1↓,
PKM2↓,
ACSL1↓,
CPT1A↓,
FASN↓,
FAO↓, Significant reduction of FAO was detected in BA-NL-treated HCT116 cells
GlucoseCon↓, glucose uptake in HCT116 cells was significantly decreased by BA-NLs
lactateProd↓, lactic acid secretion was significantly suppressed in HCT116 cells treated with BA-NLs

732- Bor,    Boron's neurophysiological effects and tumoricidal activity on glioblastoma cells with implications for clinical treatment
eff↑, many boron compounds possess direct tumoricidal activity and there is substantial evidence that certain boron compounds can cross the blood-brain barrier.
IGF-1↝,
Glycolysis↝,

1416- Bos,    Anti-cancer properties of boswellic acids: mechanism of action as anti-cancerous agent
- Review, NA, NA
5LO↓,
TumCCA↑, G0/G1 phase
LC3B↓, reduced the expression of LC3A/B-I and LC3A/B-II,
PI3K↓,
Akt↓,
Glycolysis↓,
AMPK↑,
mTOR↓,
Let-7↑,
COX2↓, methanolic extract decreased the expression of cyclooxygenase-2 gene
VEGF↓,
CXCR4↓,
MMP2↓,
MMP9↓,
HIF-1↓,
angioG↓,
TumCP↓,
TumCMig↓,
NF-kB↓,

1640- CA,  MET,    Caffeic Acid Targets AMPK Signaling and Regulates Tricarboxylic Acid Cycle Anaplerosis while Metformin Downregulates HIF-1α-Induced Glycolytic Enzymes in Human Cervical Squamous Cell Carcinoma Lines
- in-vitro, Cerv, SiHa
GLS↓, downregulation of Glutaminase (GLS) and Malic Enzyme 1 (ME1)
NADPH↓, CA alone and co-treated with Met caused significant reduction of NADPH
ROS↑, increased ROS formation and enhanced cell death
TumCD↑,
AMPK↑, activation of AMPK
Hif1a↓, Met inhibited Hypoxia-inducible Factor 1 (HIF-1α). CA treatment at 100 μM for 24 h also inhibited HIF-1α
GLUT1↓,
GLUT3↓,
HK2↓,
PFK↓, PFKFB4
PKM2↓,
LDH↓,
cMyc↓, Met suppressed the expression of c-Myc, BAX and cyclin-D1 (CCND1) a
BAX↓,
cycD1/CCND1↓,
PDH↓, CA at a concentration of 100 µM caused inhibition of PDK activity
ROS↑, CA Regulates TCA Cycle Supply via Pyruvate Dehydrogenase Complex (PDH), Induces Mitochondrial ROS Generation and Evokes Apoptosis
Apoptosis↑,
eff↑, both drugs inhibited the expression of ACLY and FAS, but the greatest effect was detected after co-treatment
ACLY↓,
FASN↓,
Bcl-2↓,
Glycolysis↓, Met acts as a glycolytic inhibitor under normoxic and hypoxic conditions

1261- CAP,    Capsaicin inhibits glycolysis in esophageal squamous cell carcinoma by regulating hexokinase‑2 expression
- in-vitro, ESCC, KYSE150
GlucoseCon↓,
lactateProd↓,
HK2↓,
Glycolysis↓,
PTEN↑,
AKT1↓, RAC‑α serine threonine‑protein kinase signaling pathway was downregulated

3869- Carno,    Carnosine, Small but Mighty—Prospect of Use as Functional Ingredient for Functional Food Formulation
- Review, AD, NA - Review, Stroke, NA
*ROS↓, carnosine scavenges reactive oxygen species (ROS)
*IronCh↑, it can chelate divalent metal ions: heavy metal chelating activity
*AntiAge↑, can slow down aging.
*antiOx↑, natural antioxidant [4] and has anti-inflammatory and neuroprotective properties
*Inflam↓,
*neuroP↑,
*lipid-P↓, Carnosine reduces lipid peroxidation, but also inhibits oxidative modification of protein exposed to hydroxyl radicals
*toxicity↓, carnosine can be recommended as a natural cure that has no side effects but is highly efficient
*NOX4↓, human kidney tubular epithelial (HK2) cells indicated that carnosine decreased NADPH oxidase (Nox) 4 expression and increased total superoxide dismutase (T-SOD) activity, thus reducing the production of intracellular ROS,
*SOD↑,
*HNE↓, Rising data indicate that carnosine acts as a scavenger of reactive and cytotoxic carbonyl species including 4-hydroxynonenal (HNE)
*IL6↓, anserine and/or carnosine supplementation significantly decreased IL-6, TNF-α, and IL-1β in pre-treated mice with MPTP-induced PD,
*TNF-α↓,
*IL1β↓,
*Sepsis↓, carnosine has a beneficial effect on reducing acute kidney injury due to septic shock
*eff↑, carnosine on ischemic stroke, there was a 29.4% average reduction in infarct volume with a clear dose-dependent effect (38.1% reduction on 1000 mg/kg dose compared with 13.2% for doses less than 500 mg/kg)
*GABA↝, In addition to the carnosine-histidine-histamine pathway, carnosine can also have a direct impact on CA1 pyramidal neurons [212] or act as a precursor for the neurotransmitter GABA
*Aβ↓, Several studies have reported that carnosine supplementation reduced β-amyloid cumulation in the hippocampus of a transgenic mouse model of AD
Glycolysis↓, carnosine has the ability to inhibit glycolysis and thus achieve an antitumor effect
AntiTum↑,
p‑Akt↓, significant reduction of Akt phosphorylation in the U87 glioblastoma cell line
TumCCA↑, Carnosine has an effect in bladder cancer by stopping the G1 phase cell cycle by increasing p21WAF1 expression and decreasing cyclin/CDK complexes
angioG↓, inhibits angiogenesis by suppressing VEGFR-2
VEGFR2↓,
NF-kB↓, suppressing nuclear factor kB (NF-κB) signaling pathway activation in human colon cancer cells

2393- Cela,    Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect
- in-vivo, Sepsis, NA - in-vitro, Nor, RAW264.7
OS↑, Cel protected mice from lethal endotoxemia and improved their survival with sepsis, and it significantly decreased the levels of pro-inflammatory cytokines in mice and macrophages treated with LPS
PKM2↓, Cel bound to Cys424 of pyruvate kinase M2 (PKM2), inhibiting the enzyme and thereby suppressing aerobic glycolysis (Warburg effect).
Glycolysis↓,
Warburg↓,
Inflam↓, Cel inhibits inflammation and the Warburg effect in sepsis via targeting PKM2 and HMGB1 protein.
HMGB1↓, Cel directly binds PKM2 and HMGB1
ALAT↓, pretreatment with Cel followed by LPS significantly reduced serum levels of ALT, AST and urea (
AST↓,
TNF-α↓, Cel pretreatment also decreased the serum levels of TNF-α, IL-1β and IL-6
IL1β↓,
IL6↓,

2398- CGA,    Polyphenol-rich diet mediates interplay between macrophage-neutrophil and gut microbiota to alleviate intestinal inflammation
- in-vivo, Col, NA
PKM2↓, Chlorogenic acid mitigated colitis by reducing M1 macrophage polarization through suppression of pyruvate kinase M 2 (Pkm2)-dependent glycolysis and inhibition of NOD-like receptor protein 3 (Nlrp3) activation
Glycolysis↓,
NLRP3↓,
Inflam↓, Anti-inflammatory effect of chlorogenic acid is mediated through PKM2-dependent glycolysis
HK2↓, hexokinase 2 (Hk2), pyruvate dehydrogenase kinase 1 (Pdk1) and lactate dehydrogenase A (Ldha), while CGA significantly decreased this up-regulated genes level in macrophages
PDK1↓,
LDHA↓,
GLUT1↓, significant reduction in the LPS-induced increased glucose transporter protein 1 (Glut1) mRNA
ECAR↓, Importantly, the enhanced extracellular acidification rates (ECRA), indicative of glycolysis, was rescued by CGA treatment

2781- CHr,  PBG,    Chrysin a promising anticancer agent: recent perspectives
- Review, Var, NA
PI3K↓, It can block Phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling in different animals against various cancers
Akt↓,
mTOR↓,
MMP9↑, Chrysin strongly suppresses Matrix metalloproteinase-9 (MMP-9), Urokinase plasminogen activator (uPA) and Vascular endothelial growth factor (VEGF), i.e. factors that can cause cancer
uPA↓,
VEGF↓,
AR↓, Chrysin has the ability to suppress the androgen receptor (AR), a protein necessary for prostate cancer development and metastasis
Casp↑, starts the caspase cascade and blocks protein synthesis to kill lung cancer cells
TumMeta↓, Chrysin significantly decreased lung cancer metastasis i
TumCCA↑, Chrysin induces apoptosis and stops colon cancer cells in the G2/M cell cycle phase
angioG↓, Chrysin prevents tumor growth and cancer spread by blocking blood vessel expansion
BioAv↓, Chrysin’s solubility, accessibility and bioavailability may limit its medical use.
*hepatoP↑, As chrysin reduced oxidative stress and lipid peroxidation in rat liver cells exposed to a toxic chemical agent.
*neuroP↑, Protecting the brain against oxidative stress (GPx) may be aided by increasing levels of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx).
*SOD↑,
*GPx↑,
*ROS↓, A decrease in oxidative stress and an increase in antioxidant capacity may result from chrysin’s anti-inflammatory properties
*Inflam↓,
*Catalase↑, Supplementation with chrysin increased the activity of antioxidant enzymes like SOD and catalase and reduced the levels of oxidative stress markers like malondialdehyde (MDA) in the colon tissue of the rats.
*MDA↓, Antioxidant enzyme activity (SOD, CAT) and oxidative stress marker (MDA) levels were both enhanced by chrysin supplementation in mouse liver tissue
ROS↓, reduction of reactive oxygen species (ROS) and oxidative stress markers in the cancer cells further indicated the antioxidant activity of chrysin
BBB↑, After crossing the blood-brain barrier, it has been shown to accumulate there
Half-Life↓, The half-life of chrysin in rats is predicted to be close to 2 hours.
BioAv↑, Taking chrysin with food may increase the effectiveness of the supplement: increased by a factor of 1.8 when taken with a high-fat meal
ROS↑, In contrast to 5-FU/oxaliplatin, chrysin increases the production of reactive oxygen species (ROS), which in turn causes autophagy by stopping Akt and mTOR from doing their jobs
eff↑, mixture of chrysin and cisplatin caused the SCC-25 and CAL-27 cell lines to make more oxygen free radicals. After treatment with chrysin, cisplatin, or both, the amount of reactive oxygen species (ROS) was found to have gone up.
ROS↑, When reactive oxygen species (ROS) and calcium levels in the cytoplasm rise because of chrysin, OC cells die.
ROS↑, chrysin is the cause of death in both types of prostate cancer cells. It does this by depolarizing mitochondrial membrane potential (MMP), making reactive oxygen species (ROS), and starting lipid peroxidation.
lipid-P↑,
ER Stress↑, when chrysin is present in DU145 and PC-3 cells, the expression of a group of proteins that control ER stress goes up
NOTCH1↑, Chrysin increased the production of Notch 1 and hairy/enhancer of split 1 at the protein and mRNA levels, which stopped cells from dividing
NRF2↓, Not only did chrysin stop Nrf2 and the genes it controls from working, but it also caused MCF-7 breast cancer cells to die via apoptosis.
p‑FAK↓, After 48 hours of treatment with chrysin at amounts between 5 and 15 millimoles, p-FAK and RhoA were greatly lowered
Rho↓,
PCNA↓, Lung histology and immunoblotting studies of PCNA, COX-2, and NF-B showed that adding chrysin stopped the production of these proteins and maintained the balance of cells
COX2↓,
NF-kB↓,
PDK1↓, After the chrysin was injected, the genes PDK1, PDK3, and GLUT1 that are involved in glycolysis had less expression
PDK3↑,
GLUT1↓,
Glycolysis↓, chrysin stops glycolysis
mt-ATP↓, chrysin inhibits complex II and ATPases in the mitochondria of cancer cells
Ki-67↓, the amounts of Ki-67, which is a sign of growth, and c-Myc in the tumor tissues went down
cMyc↓,
ROCK1↓, (ROCK1), transgelin 2 (TAGLN2), and FCH and Mu domain containing endocytic adaptor 2 (FCHO2) were much lower.
TOP1↓, DNA topoisomerases and histone deacetylase were inhibited, along with the synthesis of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and (IL-1 beta), while the activity of protective signaling pathways was increased
TNF-α↓,
IL1β↓,
CycB/CCNB1↓, Chrysin suppressed cyclin B1 and CDK2 production in order to stop cancerous growth.
CDK2↓,
EMT↓, chrysin treatment can also stop EMT
STAT3↓, chrysin block the STAT3 and NF-B pathways, but it also greatly reduced PD-L1 production both in vivo and in vitro.
PD-L1↓,
IL2↑, chrysin increases both the rate of T cell growth and the amount of IL-2

2782- CHr,    Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives
- Review, Var, NA - Review, Stroke, NA - Review, Park, NA
*antiOx↑, antioxidant, anti-inflammatory, hepatoprotective, neuroprotective
*Inflam↓, inhibitory effect of chrysin on inflammation and oxidative stress is also important in Parkinson’s disease
*hepatoP↑,
*neuroP↑,
*BioAv↓, Accumulating data demonstrates that poor absorption, rapid metabolism, and systemic elimination are responsible for poor bioavailability of chrysin in humans that, subsequently, restrict its therapeutic effects
*cardioP↑, cardioprotective [69], lipid-lowering effect [70]
*lipidLev↓,
*RenoP↑, Renoprotective
*TNF-α↓, chrysin reduces levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2).
*IL2↓,
*PI3K↓, induction of the PI3K/Akt signaling pathway by chrysin contributes to a reduction in oxidative stress and inflammation during cerebral I/R injury
*Akt↓,
*ROS↓,
*cognitive↑, Chrysin (25, 50, and 100 mg/kg) improves cognitive capacity, inflammation, and apoptosis to ameliorate traumatic brain injury
eff↑, chrysin and silibinin is beneficial in suppressing breast cancer malignancy via decreasing cancer proliferation
cycD1/CCND1↓, chrysin and silibinin induced cell cycle arrest via down-regulation of cyclin D1 and hTERT
hTERT/TERT↓,
VEGF↓, Administration of chrysin is associated with the disruption of hypoxia-induced VEGF gene expression
p‑STAT3↓, chrysin is capable of reducing STAT3 phosphorylation in hypoxic conditions without affecting the HIF-1α protein level.
TumMeta↓, chrysin is a potent agent in suppressing metastasis and proliferation of breast cancer cells during hypoxic conditions
TumCP↓,
eff↑, combination therapy of breast cancer cells using chrysin and metformin exerts a synergistic effect and is more efficient compared to chrysin alone
eff↑, combination of quercetin and chrysin reduced levels of pro-inflammatory factors, such as IL-1β, Il-6, TNF-α, and IL-10, via NF-κB down-regulation.
IL1β↓,
IL6↓,
NF-kB↓,
ROS↑, after chrysin administration, an increase occurs in levels of ROS that, subsequently, impairs the integrity of the mitochondrial membrane, leading to cytochrome C release and apoptosis induction
MMP↓,
Cyt‑c↑,
Apoptosis↑,
ER Stress↑, in addition to mitochondria, ER can also participate in apoptosis
Ca+2↑, Upon chrysin administration, an increase occurs in levels of ROS and cytoplasmic Ca2+ that mediate apoptosis induction in OC cells
TET1↑, In MKN45 cells, chrysin promotes the expression of TET1
Let-7↑, Chrysin is capable of promoting the expression of miR-9 and Let-7a as onco-suppressor factors in cancer to inhibit the proliferation of GC cells
Twist↓, Down-regulation of NF-κB, and subsequent decrease in Twist/EMT are mediated by chrysin administration, negatively affecting cervical cancer metastasis
EMT↓,
TumCCA↑, nduction of cell cycle arrest and apoptosis via up-regulation of caspase-3, caspase-9, and Bax are mediated by chrysin
Casp3↑,
Casp9↑,
BAX↑,
HK2↓, Chrysin administration (15, 30, and 60 mM) reduces the expression of HK-2 in hepatocellular carcinoma (HCC) cells to impair glucose uptake and lactate production.
GlucoseCon↓,
lactateProd↓,
Glycolysis↓, In addition to glycolysis metabolism impairment, the inhibitory effect of chrysin on HK-2 leads to apoptosis
SHP1↑, upstream modulator of STAT3 known as SHP-1 is up-regulated by chrysin
N-cadherin↓, Furthermore, N-cadherin and E-cadherin are respectively down-regulated and up-regulated upon chrysin administration in inhibiting melanoma invasion
E-cadherin↑,
UPR↑, chrysin substantially diminishes survival by ER stress induction via stimulating UPR, PERK, ATF4, and elF2α
PERK↑,
ATF4↑,
eIF2α↑,
RadioS↑, Irradiation combined with chrysin exerts a synergistic effect
NOTCH1↑, Irradiation combined with chrysin exerts a synergistic effect
NRF2↓, in reducing Nrf2 expression, chrysin down-regulates the expression of ERK and PI3K/Akt pathways—leading to an increase in the efficiency of doxorubicin in chemotherapy
BioAv↑, chrysin at the tumor site by polymeric nanoparticles leads to enhanced anti-tumor activity, due to enhanced cellular uptake
eff↑, Chrysin- and curcumin-loaded nanoparticles significantly promote the expression of TIMP-1 and TIMP-2 to exert a reduction in melanoma invasion

1143- CHr,    Chrysin inhibited tumor glycolysis and induced apoptosis in hepatocellular carcinoma by targeting hexokinase-2
- in-vitro, HCC, HepG2 - in-vivo, NA, NA - in-vitro, HCC, HepG3 - in-vitro, HCC, HUH7
HK2↓,
GlucoseCon↓,
lactateProd↓,
Glycolysis↓,
Apoptosis↑,

1274- Cin,    Cinnamon bark extract suppresses metastatic dissemination of cancer cells through inhibition of glycolytic metabolism
- vitro+vivo, BC, MDA-MB-231
TumCI↓, CBE decreased cell motility and invasion of MDA-MB-231 human breast cancer cells without affecting their cell viability
G6PD↓,
HK2↓,
Glycolysis↓, CBE suppresses metastatic dissemination of cancer cells through inhibition of glycolysis metabolism.

1593- Citrate,    Citrate Induces Apoptotic Cell Death: A Promising Way to Treat Gastric Carcinoma?
- in-vitro, GC, BGC-823 - in-vitro, GC, SGC-7901
PFK↓, citrate, a strong physiological inhibitor of phosphofructokinase (PFK)
Glycolysis↓, citrate is a strong inhibitor of glycolysis
tumCV↓, 10 mM citrate led to a nearly complete disappearance of cancer cells, and after 72 h, no cells remained viable whatever the concentration used
cl‑Casp3↑,
cl‑PARP↑,
Apoptosis↑,
ATP↓, depletion of ATP generated by citrate
ChemoSen↑, In the previous study, citrate sensitized the cells to cisplatin, a drug which was poorly efficient by itself on such cells
Mcl-1↓, In the current study, citrate reduced MCL-1 expression in both the gastric cancer lines in a dose-dependent manner, in agreement with previous observations in mesothelioma cells
glucoNG↑, citrate activates neoglucogenesis by enhancing fructose 1,6-bisphosphatase activity
FBPase↑,
OXPHOS↓, When citrate is abundant in cells, this usually means that energy production (ATP) is sufficient, so oxidative phosphorylation (OXPHOS) and the Krebs cycle are slowed down or stopped.
TCA↓, Krebs cycle are slowed down or stopped.
β-oxidation↓, concomitantly inhibits β-oxidation
HK2↓, It may inhibit HK, at least indirectly, by the physiological retroaction of glucose-6-phosphate (G6P) on HK
PDH↓, citrate may inhibit pyruvate dehydrogenase (PDH) (39), the enzyme of the Krebs cycle which links glycolysis and the tricarboxylic cycle
ROS↑, citrate could also promote the formation of reactive oxygen species (ROS) since a sudden elevation of citrate concentration inside the cell might immediately stimulate the Krebs cycle.

1591- Citrate,    The biological significance of cancer: mitochondria as a cause of cancer and the inhibition of glycolysis with citrate as a cancer treatment
- Analysis, NA, NA
Glycolysis↓, but the most effective inhibitor of glycolysis, which to date has not been used to fight cancer, is citrate, citric acid itself,
PDK1↓, citrate also inhibits the pyruvate dehydrogenase enzyme complex [17],
SDH↓, citrate also inhibits the succinate dehydrogenase enzyme of Krebs cycle [19].

1586- Citrate,    Extracellular Citrate Is a Trojan Horse for Cancer Cells
- in-vitro, Liver, HepG2
Dose?, At low concentration, citrate increased both histone H4 acetylation and lipid deposition; at high concentration, citrate inhibited both
ac‑H4↓,
lipidDe↓,
ACLY↓, Considering the strong demand for acetyl-CoA but not for OAA in tumor cells, the exogenous citrate would behave like a trojan horse that carries OAA inside the cells and reduces ACLY expression and cellular metabolism.
selectivity↑, in non-tumor cells, changes of acetylated histone level do not correspond to a change of ACLY expression, as instead shown by HepG2 cells.
*ACLY∅, In contrast, ACLY expression in IHH (normal)cells was not modified after citrate exposure, suggesting that, in this case, ACLY expression was not regulated by histone H4 acetylation
Glycolysis↓, strong inhibition of glycolysis, which leads to a decrease in NADH necessary for OAA reduction
NADH↓,
OAA↑, exogenous citrate would behave like a trojan horse that releases OAA in the cells, where it could exert its therapeutic effect also on hepatoma cells.
other↑, most important discovery is undoubtedly the demonstration that high concentrations of citrate decrease the availability of acetyl-CoA, a key molecule both in the metabolism of sugars and lipids

1585- Citrate,    Sodium citrate targeting Ca2+/CAMKK2 pathway exhibits anti-tumor activity through inducing apoptosis and ferroptosis in ovarian cancer
- in-vitro, Ovarian, SKOV3 - in-vitro, Ovarian, A2780S - in-vitro, Nor, HEK293
Apoptosis↑,
Ferroptosis↑,
Ca+2↓, Sodium citrate chelates intracellular Ca2+
CaMKII ↓, inhibits the CAMKK2/AKT/mTOR/HIF1α-dependent glycolysis pathway, thereby inducing cell apoptosis.
Akt↓,
mTOR↓,
Hif1a↓,
ROS↑, Inactivation of CAMKK2/AMPK pathway reduces Ca2+ level in the mitochondria by inhibiting the activity of the MCU, resulting in excessive ROS production.
ChemoSen↑, Sodium citrate increases the sensitivity of ovarian cancer cells to chemo-drugs
Casp3↑,
Casp9↑,
BAX↑,
Bcl-2↓,
Cyt‑c↑, co-localization of cytochrome c and Apaf-1
GlucoseCon↓, glucose consumption, lactate production and pyruvate content were significantly reduced
lactateProd↓,
Pyruv↓,
GLUT1↓, sodium citrate decreased both mRNA and protein expression levels of glycolysis-related proteins such as Glut1, HK2 and PFKP
HK2↓,
PFKP↓,
Glycolysis↓, sodium citrate inhibited glycolysis of SKOV3 and A2780 cells
Hif1a↓, HIF1α expression was decreased significantly after sodium citrate treatment
p‑Akt↓, phosphorylation of AKT and mTOR was notably suppressed after sodium citrate treatment.
p‑mTOR↓,
Iron↑, ovarian cancer cells treated with sodium citrate exhibited higher Fe2+ levels, LPO levels, MDA levels, ROS and mitochondrial H2O2 levels
lipid-P↑,
MDA↑,
ROS↑,
H2O2↑,
mtDam↑, shrunken mitochondria, an increase in mitochondrial membrane density and disruption of mitochondrial cristae
GSH↓, (GSH) levels, GPX activity and expression levels of GPX4 were significantly reduced in SKOV3 and A2780 cells with sodium citrate treatment
GPx↓,
GPx4↓,
NADPH/NADP+↓, significant elevation in the NADP+/NADPH ratio was observed with sodium citrate treatment
eff↓, Fer-1, NAC and NADPH significantly restored the cell viability inhibited by sodium citrate
FTH1↓, decreased expression of FTH1
LC3‑Ⅱ/LC3‑Ⅰ↑, sodium citrate increased the conversion of cytosolic LC3 (LC3-I) to the lipidated form of LC3 (LC3-II)
NCOA4↑, higher levels of NCOA4
eff↓, test whether Ca2+ supplementation could rescue sodium citrate-induced ferroptosis. The results showed that Ca2+ dramatically reversed the enhanced levels of MDA, LPO and ROS triggered by sodium citrate
TumCG↓, sodium citrate inhibited tumor growth by chelation of Ca2+ in vivo

1579- Citrate,    Effect of Food Additive Citric Acid on The Growth of Human Esophageal Carcinoma Cell Line EC109
- in-vitro, ESCC, Eca109
TumCP↓, higher citric acid concentrations (800, 1600 μg/ml)
e-LDH↑, incubation with either 400, 800 or 1600 µg/ml CA for 48 hours caused a significant increase (P<0.01) in LDH release by 1.67-fold, 2.79fold and 3.16-fold, respectively
MMP↓,
Ca+2?, CA level can directly regulate several metabolic pathways and increase calcium uptake from foods
PFK↓, potential inhibitor of PFK
Glycolysis↓, increasingly evidences have indicated that a high level of citrate could inhibit the glycolytic pathway

1578- Citrate,    Understanding the Central Role of Citrate in the Metabolism of Cancer Cells and Tumors: An Update
- Review, Var, NA
TCA↑,
FASN↑, Cytosolic acetyl-CoA sustains fatty acid (FA) synthesis (FAS)
Glycolysis↓,
glucoNG↑, while it enhances gluconeogenesis by promoting fructose-1,6-biphosphatase (FBPase)
PFK1↓, citrate directly inhibits the main regulators of glycolysis, phosphofructokinase-1 (PFK1) and phosphofructokinase-2 (PFK2)
PFK2↓, well-known inhibitor of PFK
FBPase↑, enhances gluconeogenesis by promoting fructose-1,6-biphosphatase (FBPase)
TumCP↓, inhibits the proliferation of various cancer cells of solid tumors (human mesothelioma, gastric and ovarian cancer cells) at high concentrations (10–20 mM),
eff↑, promoting apoptosis and the sensitization of cells to cisplatin
ACLY↓, higher concentrations (10 mM or more) decreased both acetylation and ACLY expression
Dose↑, In various cell lines, a high concentration of citrate—generally above 10 mM—inhibits the proliferation of cancer cells in a dose dependent manner
Casp3↑,
Casp2↑,
Casp8↑,
Casp9↑,
Bcl-xL↓,
Mcl-1↓,
IGF-1R↓, citrate at high concentration (10 mM) also inhibits the insulin-like growth factor-1 receptor (IGF-1R)
PI3K↓, pathways
Akt↓, activates PTEN, the key phosphatase inhibiting the PI3K/Akt pathway
mTOR↓,
PTEN↑, high dose of citrate activates PTEN
ChemoSen↑, citrate increases the sensibility of cells to chemotherapy (in particular, cisplatin)
Dose?, oral gavage of citrate sodium (4 g/kg twice a day) for several weeks (4 to 7 weeks) significantly regressed tumors

1577- Citrate,    Citric acid promotes SPARC release in pancreatic cancer cells and inhibits the progression of pancreatic tumors in mice on a high-fat diet
- in-vivo, PC, NA - in-vitro, PC, PANC1 - in-vitro, PC, PATU-8988 - in-vitro, PC, MIA PaCa-2
Apoptosis↑, citrate treatment demonstrates signifcant effcacy in promoting tumor cell apoptosis, suppressing cell proliferation, and inhibiting tumor growth in vivo
TumCP↓,
TumCG↑,
SPARC↑, citrate treatment reveal decreased glycolysis and oxygen consumption in tumor cells, increased SPARC protein expression, and the promotion of M1 polarization
Glycolysis↓,
OCR↓,
pol-M1↑, repolarizing M2 macrophages into M1 macrophages
pol-M2 MC↓, shift from the M2 phenotype to the M1 phenotype in TAMs following citrate treatment
Weight∅, no signficant changes in body weight observed between the two groups
ATP↓, decreased ATP production of pancreatic tumors in vivo
ECAR↓, signifcantly reduced glycolytic flux, glycolytic reserve, glycolytic capacity, and acidifcation rates
mitResp↓, decreased basal mitochondrial respiration
i-ATP↑, decrease in intracellular ATP levels
p65↓, citrate effectively suppressed the expression of RELA findings collectively underscore the critical role of RELA in mediating citrate's regulation of glycolysis and suppression of pancreatic cancer progression
i-Ca+2↑, inhibition of RELA resulted in a rapid elevation of intracellular calcium levels
eff↓, overexpression of RELA and SPARC knockdown attenuated the therapeutic effects of citrate

1576- Citrate,    Targeting citrate as a novel therapeutic strategy in cancer treatment
- Review, Var, NA
TCA↓, Citrate serves as a key metabolite in the tricarboxylic acid cycle (TCA cycle, also referred to as the Krebs cycle)
T-Cell↝, modulation of T cell differentiation
Glycolysis↓, Citrate directly suppresses both cell glycolysis and TCA.
PKM2↓, citrate also inhibits glycolysis via its indirect inhibition of PK
PFK2?, In addition, citrate can inhibit PFK2,
SDH↓, citrate can inhibit enzymes, such as succinate dehydrogenase (SDH) and pyruvate dehydrogenase (PDH), in the TCA cycle
PDH↓,
β-oxidation↓, Citrate also inhibits β-oxidation as it promotes the formation of malonyl-CoA, which decreases the mitochondrial transport of fatty acids by inhibiting carnitine palmitoyl transferase I (CPT I)
CPT1A↓,
FASN↑, citrate has a positive role in promoting fatty acid synthesis
Casp3↑,
Casp2↑,
Casp8↑,
Casp9↑,
cl‑PARP↑,
Hif1a↓, Notably, in AML cell line U937, citrate induces apoptosis in a dose- and time-dependent manner by regulating the expression of HIF-1α and its downstream target GLUT-1
GLUT1↓,
angioG↓, citrate can also inhibit angiogenesis
Ca+2↓, chelate calcium ions in tumor cells
ROS↓, The other potential mechanism involved in citrate-mediated promotion of cancer growth and proliferation may be through its ability to decrease the levels of reactive oxygen species (ROS) in tumor cells
eff↓, dual effects of citrate in tumors may depend on the concentrations of citrate treatment, and different concentrations may bring out completely opposite effects even in the same tumor.
Dose↓, citrate concentration (<5 mM) appears to boost tumor growth and expansion in lung cancer A549 cells. 10mM and higher inhibited cell growth.
eff↑, citrate combined with ultraviolet (UV) radiation caused activation of caspase-3 and -9 in tumor cells (
Mcl-1↓, citrate has also been found to downregulate Mcl-1
HK2↓, Citrate also inhibits the enzymes PFK1 and hexokinase II (HK II) in glycolysis in tumor cells
IGF-1R↓,
PTEN↑, citrate may exert its effect via activating PTEN pathway
citrate↓, In addition to prostate cancer, citrate levels are significantly decreased in blood of patients with lung, bladder, pancreas and esophagus cancers
Dose∅, daily oral administration of citrate for 7 weeks at dose of 4 g/kg/day reduces tumor growth of several xenograft tumors and increases significantly the numbers of tumor-infiltrating T cells with no significant side effects in mouse models
eff↑, combining citrate with other compounds such as celecoxib, cisplatin, and 3-bromo-pyruvate, and have generated promising results
eff↑, combination of low effective doses of 3-bromo-pyruvate (3BP) (15uM), an inhibitor of glycolysis, and citrate (3 mM) significantly depleted the proliferation capability and migratory power of the C6 glioma
eff↑, Zinc treatment could lead to citrate accumulation in malignant prostate cells, which could have therapeutic potential in clinical therapy of prostate cancer.
eff↑, synergistic efficacy mediated by citrate combined with current checkpoint blockade therapies with anti-CTLA4 and/or anti-PD1/PDL1 will develop alternative novel strategies for future immunotherapy.

1574- Citrate,    Citrate Suppresses Tumor Growth in Multiple Models through Inhibition of Glycolysis, the Tricarboxylic Acid Cycle and the IGF-1R Pathway
- in-vitro, Lung, A549 - in-vitro, Melanoma, WM983B - in-vivo, NA, NA
TumCG↓,
eff↑, additional benefit accrued in combination with cisplatin
T-Cell↑, significantly higher infiltrating T-cells
p‑IGF-1R↓, citrate inhibited IGF-1R phosphorylation
p‑Akt↓, inhibited AKT phosphorylation
PTEN↑, activated PTEN
p‑eIF2α↑, increased expression of p-eIF2a p-eIF2a was decreased when PTEN was depleted
OCR↓, citrate treatment of A549 cells dramatically reduced oxygen consumption
ROS↓, observed a decrease in ROS in A549
ECAR∅, acidification rate (ECAR) and found it to be unchanged
IL1↑, s (e.g. interleukin-1, tumor necrosis factor-alpha, etc) and anti-inflammatory cytokines (e.g. interleukin-10 and interleukin 1 receptor antagonist) are activated
TNF-α↑,
IL10↑,
IGF-1R↓, Citrate Inhibits IGF-1R Activation And Its Downstream Pathway
eIF2α↑, eIF2α activity was increased in A549 cells after citrate treatment
PTEN↑, PTEN was activated
TCA↓,
Glycolysis↓, citrate may inhibit tumor growth via inhibiting glycolysis and the TCA cycle and that this effect appears to be selective to tumor tissue.
selectivity↑, citrate may inhibit tumor growth via inhibiting glycolysis and the TCA cycle and that this effect appears to be selective to tumor tissue.
*toxicity∅, Chronic citrate treatment was non-toxic as evidenced by gross pathology in numerous organs (liver, lung, spleen and kidney)
Dose∅, corresponding to approximately 56 g of citrate in a 70 kg person

2304- CUR,    Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition
- in-vitro, Lung, H1299 - in-vitro, BC, MCF-7 - in-vitro, Cerv, HeLa - in-vitro, Pca, PC3 - in-vitro, Nor, HEK293
Glycolysis↓, curcumin inhibits glucose uptake and lactate production (Warburg effect) in a variety of cancer cell lines
GlucoseCon↓,
lactateProd↓,
PKM2↓, by down-regulating PKM2 expression, via inhibition of mTOR-HIF1α axis.
mTOR↓,
Hif1a↓,
selectivity↑, however, no appreciable decrease in Warburg effect was observed in HEK 293 cells
Dose↝, Dose-dependent decrease in Warburg effect started at 2.5 μM with maximal decrease at 20 μM curcumin.
tumCV↓, Curcumin decreases viability of cancer cells

2305- CUR,    Mitochondrial targeting nano-curcumin for attenuation on PKM2 and FASN
- in-vitro, BC, MCF-7
BioAv↑, This nano-curcumin can readily enter mitochondrion in MCF-7 cancer cells.
PKM2↓, expression of both pyruvate kinase M2 and fatty acid synthase in the MCF-7 cancer cells were noticeably inhibited by CUR@DNA-FeS2-DA
FASN↓,
Glycolysis↓,

2307- CUR,    Cell-Type Specific Metabolic Response of Cancer Cells to Curcumin
- in-vitro, Colon, HT29 - in-vitro, Laryn, FaDu
PKM2↓, Siddiqui et al. have recently reported that curcumin downregulates PKM2 expression in cancer cells, consequently decreasing the Warburg effect.
Warburg↓,
mTOR↓, pKM2 downregulation coincided with the inhibition of the mammalian target of rapamycin (mTOR) pathway and consequential downregulation of hypoxia-inducible factor 1-alpha HIF1α
Hif1a↓,
Glycolysis↓, showed that a decrease of PKM2 (mediated by curcumin or by targeted PKM2 silencing) significantly reduces aerobic glycolysis and is also consequential for cell survival.

990- CUR,    Curcumin inhibits aerobic glycolysis and induces mitochondrial-mediated apoptosis through hexokinase II in human colorectal cancer cells in vitro
- in-vitro, CRC, HCT116 - in-vitro, CRC, HT-29
HK2↓,
Glycolysis↓,
Apoptosis↑,

1878- DCA,  5-FU,    Synergistic Antitumor Effect of Dichloroacetate in Combination with 5-Fluorouracil in Colorectal Cancer
- in-vitro, CRC, LS174T - in-vitro, CRC, LoVo - in-vitro, CRC, SW-620 - in-vitro, CRC, HT-29
tumCV↓, DCA inhibited the viability of CRC cells and had synergistic antiproliferation in combination with 5-FU
eff↑, synergistic antiproliferation in combination with 5-FU
PDKs↓, Dichloroacetate (DCA) is a prototypical inhibitor of mitochondrial PDK
lactateProd↓, DCA decreases lactate production by shifting the metabolism of pyruvate from glycolysis towards oxidation in the mitochondria
Glycolysis↓,
mitResp↑, DCA restored mitochondrial function
TumCCA↑, DCA potentiated the cell cycle arrest in G1 phase.
Bcl-2↓, DCA and 5-FU decreased Bcl-2 expression significantly as compared with DCA or 5-FU alone
BAX↑, Bax and caspase-3 were significantly increased in the four CRC cell lines treated with combination of DCA and 5-FU compared to their single usage
Casp3↑,

1877- DCA,    Non-Hodgkin′s Lymphoma Reversal with Dichloroacetate
- Case Report, lymphoma, NA
Remission↑, Refusing all suggested chemotherapies, the patient began self-administering dichloroacetate (DCA) 900 mg daily with a PET scan showing complete remission four months later.
p‑PDKs↓, DCA has been shown to block this phosphorylation by PDK at the mitochondrial membrane level and decrease glycolysis in favor of glucose oxidation
Glycolysis↓,
i-Ca+2↓, This return to a normal metabolism of glucose allows for major changes including a decrease in Ca++ intracellularly, and stabilization of the mitochondria allowing a reactivation of caspases in cancer cells leading to apoptosis
toxicity↓, A reversible, minimal nerve damage can be considerably reduced by a daily thiamine intake of several hundred milligrams for humans. thiamine amount varies from 50 mg/day to 100 mg/day depending on whether it is administered orally or injected
Dose∅, A Non-Hodgkin′s lymphoma patient taking 10 mg/kg [750 mg] of dichloroacetate daily of his own accord, had a complete remission of his Non-Hodgkin′s lymphoma cancer after four months

1876- DCA,  Chemo,    In vitro cytotoxicity of novel platinum-based drugs and dichloroacetate against lung carcinoid cell lines
- in-vivo, Lung, H727
eff↑, DCA (10 mM) inhibited the growth of UMC- 11 cells by 22% and sensitised these highly resistant cells to carboplatin, satraplatin and JM118 1.4-2.4-fold.
TumCG↓,
Glycolysis↓, DCA that promotes mitochondrial respiration over aerobic glycolysis
mitResp↑,

1875- DCA,    Dichloroacetate inhibits neuroblastoma growth by specifically acting against malignant undifferentiated cells
- in-vitro, neuroblastoma, NA - in-vivo, NA, NA
selectivity↑, acting specifically on the mitochondria of cancer cells without perturbing the physiology of nonmalignant cells.
AntiCan↑, DCA exhibits an unexpected anticancer effect on NB tumor cells
TumVol↓, growth inhibition became statistically significant when mice were treated with 25 mg/kg/dose of DCA (55% of reduction compared with control group)
PDKs↓, effects of DCA are related to PDK inhibition, mitochondrial oxidative phosphorylation activation and specific mitochondrial hyperpolarization reduction,
mt-OXPHOS↑,
MMP↓,
Glycolysis↓, shifting cellular metabolism from glycolysis to glucose oxidation, without any deleterious effect on normal cells.
toxicity↓, Indeed, more than 40 clinical trials of DCA report that the most significant adverse effect of long-term DCA administration is a reversible peripherical neuropathy.
Warburg↓, indeed, DCA is able to reverse the Warburg effect by inhibiting PDK, restoring mitochondrial membrane potential and increasing ROS production.
ROS↑,
eff↑, DCA was celebrated as the magic bullet against cancer, even if it is currently not yet approved for cancer treatment.

1866- DCA,  MET,  BTZ,    Targeting metabolic pathways alleviates bortezomib-induced neuropathic pain without compromising anticancer efficacy in a sex-specific manner
- in-vivo, NA, NA
eff↑, Metformin, DCA, and oxamate effectively attenuated bortezomib-induced neuropathic pain without compromising the anticancer efficacy of bortezomib in both male and female mice.
TumCG↓,
Hif1a↓, Metformin, a widely used antidiabetic drug, has been shown to inhibit the expression of HIF1A
PDH↑, Dichloroacetate (DCA), a small molecule inhibitor, targets PDHK, thereby activating PDH and promoting the entry of pyruvate into the mitochondrial Krebs cycle
lactateProd↓, Oxamate, an analog of pyruvate, inhibits lactate dehydrogenase, thereby reducing the production of lactate and attenuating the pain-inducing effects of extracellular acidification (25) in mice with bortezomib-induced neuropathic pain (4
TumVol↓,
TumW↓,
Glycolysis↑, These findings suggest that targeting aerobic glycolysis with DCA or oxamate can complement the anticancer efficacy of bortezomib in male tumor-bearing mice.
neuroP↑, Metformin and aerobic glycolysis inhibitors attenuate bortezomib-induced neuropathic pain without compromising anticancer efficacy in female tumor-bearing mice

1889- DCA,    A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth
- Review, Var, NA
PDKs↓, Dichloroacetate (DCA) inhibits mitochondrial pyruvate dehydrogenase kinase (PDK)
Glycolysis↓, shifts metabolism from glycolysis to glucose oxidation
mt-H2O2↑, increases mitochondrial H2O2
Apoptosis↑, DCA induces apoptosis, decreases proliferation, and inhibits tumor growth, without apparent toxicity
TumCP↓,
TumCG↓,
toxicity∅,

1885- DCA,    Role of SLC5A8, a plasma membrane transporter and a tumor suppressor, in the antitumor activity of dichloroacetate
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW-620 - in-vitro, CRC, HT-29
SMCT1∅, SLC5A8 transports dichloroacetate very effectively with high affinity. This transporter is expressed in normal cells, but the expression is silenced in tumor cells via epigenetic mechanisms.
eff↓, lack of the SLC5A8 transporter makes tumor cells resistant to the antitumor activity of dichloroacetate.
eff↑, However, if the transporter is expressed in tumor cells ectopically, the cells become sensitive to the drug at low concentrations. This is evident in breast cancer cells, colon cancer cells, and prostate cancer cells.
eff↑, our findings suggest that combining dichloroacetate with a DNA methylation inhibitor would offer a means to reduce the doses of dichloroacetate to avoid detrimental effects associated with high doses but without compromising antitumor activity.
PDKs↓, Dichloroacetate is an inhibitor of pyruvate dehydrogenase kinase (PDK), which phosphorylates the E1α subunit of PDC and inactivates the complex
MMP↓, depolarization of the mitochondrial membrane,
Glycolysis↓, suppression of glycolysis
mitResp↑, enhancement of mitochondrial oxidation
ROS↑, production of reactive oxygen species,
eff↑, In control cells, which did not express the transporter, dichloroacetate did not have any significant effect. However, under identical conditions, SLC5A8-expressing cells underwent apoptosis to a marked extent. This phenomenon was seen in all three c

5196- DCA,    Dichloroacetate induces apoptosis in endometrial cancer cells
- in-vitro, Var, NA
selectivity↑, Initiation of apoptosis was observed in five low to moderately invasive cancer cell lines including Ishikawa, RL95-2, KLE, AN3CA, and SKUT1B while treatment had no effect on non-cancerous 293T cells.
MMP↓, a decrease in mitochondrial membrane potential, and decreased Survivin transcript abundance, which are consistent with a mitochondrial-regulated mechanism.
survivin↓,
Ca+2↓, DCA treatment decreased intracellular calcium levels in most apoptotic responding cell lines which suggests a contribution from the NFAT-Kv1.5-mediated pathway.
P53↑, DCA treatment increased p53 upregulated modulator of apoptosis (PUMA) transcripts in cell lines with an apoptotic response, suggesting involvement of a p53-PUMA-mediated mechanism.
PDK1↓, DCA binds to PDK and attenuates inhibition of PDH activity.
PDH↑,
Glycolysis↓, The increased PDH activity shifts metabolism from glycolysis to glucose oxidation and decreases mitochondrial membrane potential (MMP) hyperpolarization
OXPHOS↑,
ROS↑, translocation of reactive oxygen species (ROS) and cytochrome c from the mitochondria to the cytoplasm, subsequently inducing apoptosis through the activation of caspases
Cyt‑c↑,
Apoptosis↑,
Casp↑,
tumCV↓, DCA Reduces Endometrial Cancer Cell Viability in a Dose-Dependent Manner
PUMA↑, DCA Increases PUMA Expression

5197- DCA,  5-FU,    Dichloroacetate attenuates hypoxia-induced resistance to 5-fluorouracil in gastric cancer through the regulation of glucose metabolism
- in-vitro, GC, NA
Glycolysis↓, dichloroacetate (DCA), an inhibitor of the glycolytic pathway.
ChemoSen↑, DCA treatment was able to re-sensitize gastric cancer cells with hypoxia-induced resistance to 5-FU through the alteration of glucose metabolism.
PDK1↓, Dichloroacetate (DCA) is a well-known inhibitor of PDK

4901- DCA,  Sal,    Dichloroacetate and Salinomycin as Therapeutic Agents in Cancer
- Review, NSCLC, NA
Glycolysis↓, DCA redirects mitochondrial metabolism away from glycolysis to OXPHOS by the inhibition of PDKs
OXPHOS↑,
PDKs↓,
ROS↑, DCA increases reactive oxygen species (ROS), which induce downstream changes in mitochondrial function, causing the selective apoptosis of cancer cells.
Apoptosis↑,
GlucoseCon↓, treatment with DCA decreased glucose consumption and lactate production in vitro in a manner that was statistically significant compared to the controls
lactateProd↓,
RadioS↑, it enhanced the sensitivity of A549 and H1299 cells to X-ray-induced cell killing
TumAuto↑, DCA has been shown to induce autophagy instead of inhibiting it.
mTOR↓, The DCA-induced induction of autophagy was found to be mediated by the generation of ROS, the inhibition of the mammalian targets of rapamycin (mTOR),
LC3s↓, Lu and colleagues found that LC3 decreased while p62 levels increased, both of which are hallmarks of autophagy inhibition
p62↑,
TumCG↓, In vivo studies have demonstrated that DCA inhibits the growth of A549 and H1975 tumor xenografts and enhances the survival of tumor-bearing nude mice
OS↑,
toxicity↝, the most clinically limiting side effect of DCA is peripheral neuropathy
ChemoSen↑, DCA exerts synergistic potential with the most widely used chemotherapy agent, paclitaxel, on NSCLC cells.
eff↑, DCA has also been shown to have anticancer synergies with various non-traditional agents, the most prominent of which is metformin.
eff↑, Another compound that DCA has been shown to have a strong synergism with is ivermectin.
Ferritin↓, SAL and its derivatives prevent the movement of iron from the lumen to the cytosol, triggering an iron-depletion reaction that is characterized by the rapid degradation of ferritin
CSCs↓, SAL has been shown to selectively target CSCs in vitro and in vivo, but its mode of action is not fully understood.
EMT↓, SAL has also been shown to suppress the epithelial–mesenchymal transition (EMT) as well as transforming growth factors (TGFs). EMT is a process that is pivotal to metastasis.
ROS↑, SAL triggers apoptosis by elevating intracellular ROS levels, leading to the translocation of Bax protein to the mitochondria, cytochrome c (Cytc) release, and the activation of caspase-3
Cyt‑c↑,
Casp3↑,
ER Stress↑, SAL was observed to upregulate ER stress-related proteins in a time-/dose-dependent manner
selectivity↑, SAL induced cell death in multiple apoptosis-resistant cancer cell lines, but not in normal healthy human cells
eff↑, Skeberdytė and colleagues were among the first to recognize that DCA had synergistic potential with SAL.
TumCG↓, DCA and SAL were found to significantly suppress tumor growth in vivo in the mice.

1863- dietFMD,  Chemo,    Effect of fasting on cancer: A narrative review of scientific evidence
- Review, Var, NA
eff↑, recommend combining prolonged periodic fasting with a standard conventional therapeutic approach to promote cancer‐free survival, treatment efficacy, and reduce side effects in cancer patients.
ChemoSideEff↓, lowered levels of IGF1 and insulin have the potential to protect healthy cells from side effects
ChemoSen↑,
Insulin↓, causes insulin levels to drop and glucagon levels to rise
HDAC↓, Histone deacetylases are inhibited by ketone bodies, which may slow tumor development.
IGF-1↓, FGF21 rises during intermittent fasting, and it plays a vital role in lowering IGF1 levels by inhibiting phosphorylated STAT5 in the liver
STAT5↓,
BG↓, Fasting suppresses glucose, IGF1, insulin, the MAPK pathway, and heme oxygenase 1
MAPK↓,
HO-1↓,
ATG3↑, while increasing many autophagy‐regulating components (Atgs, LC3, Beclin1, p62, Sirt1, and LAMP2).
Beclin-1↑,
p62↑,
SIRT1↑,
LAMP2↑,
OXPHOS↑, Fasting causes cancer cells to release oxidative phosphorylation (OXPHOS) through aerobic glycolysis
ROS↑, which leads to an increase in reactive oxygen species (ROS), p53 activation, DNA damage, and cell death in response to chemotherapy.
P53↑,
DNAdam↑,
TumCD↑,
ATP↑, and causes extracellular ATP accumulation, which inhibits Treg cells and the M2 phenotype while activating CD8+ cytotoxic T cells.
Treg lymp↓,
M2 MC↓,
CD8+↑,
Glycolysis↓, By lowering glucose intake and boosting fatty acid oxidation, fasting can induce a transition from aerobic glycolysis to mitochondrial oxidative phosphorylation in cancerous cells, resulting in increased ROS
GutMicro↑, Fasting has been shown to have a direct impact on the gut microbial community's constitution, function, and interaction with the host, which is the complex and diverse microbial population that lives in the intestine
GutMicro↑, Fasting also reduces the number of potentially harmful Proteobacteria while boosting the levels of Akkermansia muciniphila.
Warburg↓, Fasting generates an anti‐Warburg effect in colon cancer models, which increases oxygen demand but decreases ATP production, indicating an increase in mitochondrial uncoupling.
Dose↝, Those patients fasted for 36 h before treatment and 24 h thereafter, having a total of 350 calories per day. Within 8 days of chemotherapy, no substantial weight loss was recorded, although there was an improvement in quality of life and weariness.

1854- dietFMD,    How Far Are We from Prescribing Fasting as Anticancer Medicine?
- Review, Var, NA
ChemoSideEff↓, ample nonclinical evidence indicating that fasting can mitigate the toxicity of chemotherapy and/or increase the efficacy of chemotherapy.
ChemoSen↑, Fasting-Induced Increase of the Efficacy of Chemotherapy
IGF-1↓,
IGFBP1↑, biological activity of IGF-1 is further compromised due to increased levels of insulin-like growth factor binding protein 1 (IGFBP1)
adiP↑, increased levels of adiponectin stimulate the fatty acid breakdown.
glyC↓, After depletion of stored glycogen, which occurs usually 24 h after initiation of fasting, the fatty acids serve as the main fuels for most tissues
E-cadherin↑, upregulation of E-cadherin expression via activation of c-Src kinase
MMPs↓, decrease of cytokines, chemokines, metalloproteinases, growth factors
Casp3↑, increase of level of activated caspase-3
ROS↑, it is postulated that the beneficial effects of fasting are ascribed to rapid metabolic and immunological response, triggered by a temporary increase in oxidative free radical production
ATP↓, Glucose deprivation leads to ATP depletion, resulting in ROS accumulation
AMPK↑, Additionally, ROS activate AMPK
mTOR↓, Under conditions of glucose deprivation, AMPK inhibits mTORC1
ROS↑, Beyond glucose deprivation, another mechanism increasing ROS levels is the AA (amino acids) starvation
Glycolysis↓, Indeed, in cancer cells, limited glucose sources impair glycolysis, decrease glycolysis-based NADPH production due to reduced utilization of the pentose phosphate pathway [88,89,90,91],
NADPH↓,
OXPHOS↝, and shift the metabolism from glycolysis to oxidative phosphorylation (OXPHOS) (“anti-Warburg effect”), leading to ROS overload [92,93,94,95].
eff↑, Fasting compared to long-term CR causes a more profound decrease in insulin (90% versus 40%, respectively) and blood glucose (50% versus 25%, respectively).
eff↑, FMD have been demonstrated to result in alterations of the serum levels of IGF-I, IGFBP1, glucose, and ketone bodies reminiscent of those observed in fasting
*RAS↓, A plausible explanation of the differential protective effect of fasting against chemotherapy is the attenuation of the Ras/MAPK and PI3K/Akt pathways downstream of decreased IGF-1 in normal cells
*MAPK↓,
*PI3K↓,
*Akt↓,
eff↑, Starvation combined with cisplatin has been shown in vitro to protect normal cells, promoting complete arrest of cellular proliferation mediated by p53/p21 activation in AMPK-dependent and ATM-independent manner
ROS↑, generation of ROS due to paradoxical activation of the AKT/S6K, partially via the AMPK-mTORC1 energy-sensing pathways malignant cells
Akt↑, cancer cells
Casp3↑, combination of fasting and chemotherapy was in part ascribed to enhanced apoptosis due to activation of caspase 3

1861- dietFMD,  Chemo,    Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models
- in-vitro, Colon, CT26 - in-vivo, NA, NA
selectivity↑, Short-term-starvation (STS) was shown to protect normal cells and organs but to sensitize different cancer cell types to chemotherapy
ChemoSen↑, STS potentiated the effects of OXP on the suppression of colon carcinoma growth and glucose uptake in both in vitro and in vivo models.
BG↓, glucose and amino acid deficiency conditions imposed by STS promote an anti-Warburg effect
AminoA↓,
Warburg↓,
OCR↑, characterized by increased oxygen consumption but failure to generate ATP, resulting in oxidative damage and apoptosis.
ATP↓,
ROS↑, a significant increase in O2consumption rate (OCR), indicative of an increased oxidative metabolism, was observed
Apoptosis↑,
GlucoseCon↓, STS was as effective as oxaliplatin (OXP) in reducing the average tumor glucose consumption
PI3K↓, STS and in particular STS+OXP down-regulated the expression of PI3K
PTEN↑, and up-regulated PTEN expression
GLUT1↓, STS induced a profound reduction in GLUT1 , GLUT2 , HKII , PFK1, PK
GLUT2↓,
HK2↓,
PFK1↓,
PKA↓,
ATP:AMP↓, Accordingly, the ATP/AMP ratio, a good indicator of cellular energy charge, was dramatically reduced by the two STS settings
Glycolysis↓, results strongly support the effect of STS on reducing glycolysis and lactate production and increasing respiration at Complexes I-IV resulting in superoxide production/oxidative stress but in reduced ATP generation.
lactateProd↓,

2272- dietMet,    Methionine restriction - Association with redox homeostasis and implications on aging and diseases
- Review, Nor, NA
*OS↑, MR seems to be an approach to prolong lifespan which has been validated extensively in various animal models
*mt-ROS↓, Mitochondrial ROS reduction by methionine restriction (MR) maintains redox balance
*H2S↑, MR ameliorates oxidative stress by autophagy activation and hepatic H2S generation.
*FGF21↑, MR impact on cognition by upregulation of FGF21 and alterations of gut microbiome.
*cognitive↑,
*GutMicro↑,
*IGF-1↓, long-term, low-fat, whole-food vegan diet may increase life expectancy in humans by down-regulating IGF-I activity
*mTOR↓, Suppression of the mTOR pathway by MR can also lead to increased H2S production,
*GSH↑, 80% MR increases the GSH content in erythrocytes of rats,
*SOD↑, A diet restricting methionine to 80% (0.17% Met) significantly increases plasma SOD and decreases MDA levels while increasing mRNA expression of Nrf2, HO-1, and NQO-1 in the heart of HFD-fed mice with cardiovascular impairment
*MDA↓,
*NRF2↑,
*HO-1↑,
*NQO1↑,
*GLUT4↑, In skeletal muscle, MR improved expression and transport of GLUT4 and glycogen levels and increased the expression of glycolysis-related genes (HK2, PFK, PKM) in HFD-fed mice
*Glycolysis↑,
*HK2↑,
*PFK↑,
*PKM2↑,
*GlucoseCon↑, promoting glucose uptake and glycogen synthesis, glycolysis, and aerobic oxidation in skeletal muscle.
*ATF4↑, MR can increase the expression of hepatic FGF21 by activating GCN2/ATF4/PPARα signaling in liver cells, thereby improving insulin sensitivity, accelerating energy expenditure, and promoting fat oxidation and glucose metabolism
*PPARα↑,
GSH↓, MR was able to decrease GSH in HepG2 cells, thereby regulating the activation state of protein tyrosine phosphatases such as PTEN.
GSTs↑, decrease of GSH by MR also triggers upregulation of glutathione S-transferase
ROS↑, Double deprivation of methionine and cystine both in vitro and in vivo resulted in a decrease in GSH content, an increase in ROS levels, and an induction of autophagy in glioma cells
*neuroP↑, A neuroprotective role of FGF21

1605- EA,    Ellagic Acid and Cancer Hallmarks: Insights from Experimental Evidence
- Review, Var, NA
*BioAv↓, Within the gastrointestinal tract, EA has restricted bioavailability, primarily due to its hydrophobic nature and very low water solubility.
antiOx↓, strong antioxidant properties [12,13], anti-inflammatory effects
Inflam↓,
TumCP↓, numerous studies indicate that EA possesses properties that can inhibit cell proliferation
TumCCA↑, achieved this by causing cell cycle arrest at the G1 phase
cycD1/CCND1↓, reduction of cyclin D1 and E levels, as well as to the upregulation of p53 and p21 proteins
cycE/CCNE↓,
P53↑,
P21↑,
COX2↓, notable reduction in the protein expression of COX-2 and NF-κB as a result of this treatment
NF-kB↓,
Akt↑, suppressing Akt and Notch signaling pathways
NOTCH↓,
CDK2↓,
CDK6↓,
JAK↓, suppression of the JAK/STAT3 pathway
STAT3↓,
EGFR↓, decreased expression of epidermal growth factor receptor (EGFR)
p‑ERK↓, downregulated the expression of phosphorylated ERK1/2, AKT, and STAT3
p‑Akt↓,
p‑STAT3↓,
TGF-β↓, downregulation of the TGF-β/Smad3
SMAD3↓,
CDK6↓, EA demonstrated the capacity to bind to CDK6 and effectively inhibit its activity
Wnt/(β-catenin)↓, ability of EA to inhibit phosphorylation of EGFR
Myc↓, Myc, cyclin D1, and survivin, exhibited decreased levels
survivin↓,
CDK8↓, diminished CDK8 level
PKCδ↓, EA has demonstrated a notable downregulatory impact on the expression of classical isoenzymes of the PKC family (PKCα, PKCβ, and PKCγ).
tumCV↓, EA decreased cell viability
RadioS↑, further intensified when EA was combined with gamma irradiation.
eff↑, EA additionally potentiated the impact of quercetin in promoting the phosphorylation of p53 at Ser 15 and increasing p21 protein levels in the human leukemia cell line (MOLT-4)
MDM2↓, finding points to the ability of reduced MDM2 levels
XIAP↓, downregulation of X-linked inhibitor of apoptosis protein (XIAP).
p‑RB1↓, EA exerted a decrease in phosphorylation of pRB
PTEN↑, EA enhances the protein phosphatase activity of PTEN in melanoma cells (B16F10)
p‑FAK↓, reduced phosphorylation of focal adhesion kinase (FAK)
Bax:Bcl2↑, EA significantly increases the Bax/Bcl-2 rati
Bcl-xL↓, downregulates Bcl-xL and Mcl-1
Mcl-1↓,
PUMA↑, EA also increases the expression of Bcl-2 inhibitory proapoptotic proteins PUMA and Noxa in prostate cancer cells
NOXA↑,
MMP↓, addition to the reduction in MMP, the release of cytochrome c into the cytosol occurs in pancreatic cancer cells
Cyt‑c↑,
ROS↑, induction of ROS production
Ca+2↝, changes in intracellular calcium concentration, leading to increased levels of EndoG, Smac/DIABLO, AIF, cytochrome c, and APAF1 in the cytosol
Endoglin↑,
Diablo↑,
AIF↑,
iNOS↓, decreased expression of Bcl-2, NF-кB, and iNOS were observed after exposure to EA at concentrations of 15 and 30 µg/mL
Casp9↑, increase in caspase 9 activity in EA-treated pancreatic cancer cells PANC-1
Casp3↑, EA-induced caspase 3 activation and PARP cleavage in a dose-dependent manner (10–100 µmol/L)
cl‑PARP↑,
RadioS↑, EA sensitizes and reduces the resistance of breast cancer MCF-7 cells to apoptosis induced by γ-radiation
Hif1a↓, EA reduced the expression of HIF-1α
HO-1↓, EA significantly reduced the levels of two isoforms of this enzyme, HO-1, and HO-2, and increased the levels of sEH (Soluble epoxide hydrolase) in LnCap
HO-2↓,
SIRT1↓, EA-induced apoptosis was associated with reduced expression of HuR and Sirt1
selectivity↑, A significant advantage of EA as a potential chemopreventive, anti-tumor, or adjuvant therapeutic agent in cancer treatment is its relative selectivity
Dose∅, EA significantly reduced the viability of cancer cells at a concentration of 10 µmol/L, while in healthy cells, this effect was observed only at a concentration of 200 µmol/L
NHE1↓, EA had the capacity to regulate cytosolic pH by downregulating the expression of the Na+/H+ exchanger (NHE1)
Glycolysis↓, led to intracellular acidification with subsequent impairment of glycolysis
GlucoseCon↓, associated with a decrease in the cellular uptake of glucose
lactateProd↓, notable reduction in lactate levels in supernatant
PDK1?, inhibit pyruvate dehydrogenase kinase (PDK) -bind and inhibit PDK3
PDK1?,
ECAR↝, EA has been shown to influence extracellular acidosis
COX1↓, downregulation of cancer-related genes, including COX1, COX2, snail, twist1, and c-Myc.
Snail↓,
Twist↓,
cMyc↓,
Telomerase↓, EA, might dose-dependently inhibit telomerase activity
angioG↓, EA may inhibit angiogenesis
MMP2↓, EA demonstrated a notable reduction in the secretion of matrix metalloproteinase (MMP)-2 and MMP-9.
MMP9↓,
VEGF↓, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
Dose↝, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
PD-L1↓, EA downregulated the expression of the immune checkpoint PD-L1 in tumor cells
eff↑, EA might potentially enhance the efficacy of anti-PD-L1 treatment
SIRT6↑, EA exhibited statistically significant upregulation of sirtuin 6 at the protein level in Caco2 cells
DNAdam↓, increase in DNA damage

1612- EA,    Negative Effect of Ellagic Acid on Cytosolic pH Regulation and Glycolytic Flux in Human Endometrial Cancer Cell
- in-vitro, EC, NA
NHE1↓, 48 hour treatment with Ellagic acid (20 µM) significantly decreased NHE1 transcript levels by 75%, NHE1 protein abundance by 95%
i-pH↓, pHi from 7.24 ± 0.01 to 7.02 ± 0.01
ROS↓, ROS by 82%
GlucoseCon↓, glucose uptake by 58%
NHE1↓, Treatment with EA is followed by a significant decline of NHE1 transcript levels, NHE1 protein abundance, and Na+/H+ exchanger activity.
Glycolysis↓, EA down-regulates expression and function of the Na+/H+ exchanger, decreases cytosolic acidification with subsequent impairment of glycolysis

989- EGCG,  Citrate,    In vitro and in vivo study of epigallocatechin-3-gallate-induced apoptosis in aerobic glycolytic hepatocellular carcinoma cells involving inhibition of phosphofructokinase activity
- in-vitro, HCC, NA - in-vivo, NA, NA
PFK↓,
Glycolysis↓, only inhibited glycolysis in cancer cells with a high rate of aerobic glycolysis (HCC-LM3 and HepG2 cells) but not in low-glycolytic cells (Huh-7 and LO2 cells).
lactateProd↓,
GlucoseCon↓,
TumCP↓,
TumCCA↑, arrests cells in S Phage
Casp3↑, citrate enhanced the EGCG upregulation of active caspase-3 and cleaved-PARP in both HCC-LM3 and HepG2 cells
cl‑PARP↑,
Apoptosis↑,
Casp8↑,
Casp9↑,
Cyt‑c↝, translocation of cytochrome c from the mitochondria into the cytosol
MMP↓,
BAD↑,
GLUT2↓, figure2 c,d
PKM2∅, figure2 c,d

937- EGCG,    Metabolic Consequences of LDHA inhibition by Epigallocatechin Gallate and Oxamate in MIA PaCa-2 Pancreatic Cancer Cells
- in-vitro, Pca, MIA PaCa-2
lactateProd↓, significantly reduced lactate production
Glycolysis↓,
GlucoseCon↓,
LDHA↓,

649- EGCG,  CUR,  PI,    Targeting Cancer Hallmarks with Epigallocatechin Gallate (EGCG): Mechanistic Basis and Therapeutic Targets
- Review, Var, NA
*BioEnh↑, increase EGCG bioavailability is using other natural products such as curcumin and piperine
EGFR↓,
HER2/EBBR2↓,
IGF-1↓,
MAPK↓,
ERK↓, reduction in ERK1/2 phosphorylation
RAS↓,
Raf↓, Raf-1
NF-kB↓, Numerous investigations have proven that EGCG has an inhibitory effect on NF-κB
p‑pRB↓, EGCG were displayed to reduce the phosphorylation of Rb, and as a result, cells were arrested in G1 phase
TumCCA↑, arrested in G1 phase
Glycolysis↓, EGCG has been found to inhibit key enzymes involved in glycolysis, such as hexokinase and pyruvate kinase, thereby disrupting the Warburg effect and inhibiting tumor cell growth
Warburg↓,
HK2↓,
Pyruv↓,

694- EGCG,    Matcha green tea (MGT) inhibits the propagation of cancer stem cells (CSCs), by targeting mitochondrial metabolism, glycolysis and multiple cell signalling pathways
- in-vitro, BC, MCF-7
Glycolysis↓, MGT might similarly act as a glycolysis inhibitor
GAPDH↓,
ROS↑, Tea cathechins may act both as anti-oxidant and as pro-oxidants
OCR↓,
ECAR↓,
mTOR↓,
OXPHOS↓,

2302- EGCG,    Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
- Review, Var, NA
TumCP↓, EGCG suppressed proliferation and dose-dependently inhibited the expression of HIF-1α
Hif1a↓, EGCG significantly suppressed HIF-1α protein accumulation in these cells but did not affect HIF-1α mRNA expression.
LDHA↓, Moreover, EGCG attenuated LDHA release in Sarcoma 180 tumor-bearing mice
PFK↓, Moreover, EGCG inhibited the expression and activity of PFK in hepatocellular carcinoma (HCC-LM3 and HepG2) cells
cardioP↑, EGCG-exerted heart benefits related to reduced LDH release
Glycolysis↓, EGCG inhibits glycolysis (especially PFK activity) in aerobic glycolytic HCC cell lines
PKM2↓, EGCG inhibits glycolysis through repressing rate-limiting enzymes (PFK and PKM2)

2309- EGCG,  Chemo,    Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts
- in-vitro, PC, MIA PaCa-2 - in-vitro, Nor, HPNE - in-vitro, PC, PANC1 - in-vivo, NA, NA
TumCG↓, EGCG reduced pancreatic cancer cell growth in a concentration-dependent manner
eff↑, and the growth inhibition effect was further enhanced under glucose deprivation conditions.
ROS↑, EGCG at 40 µM increased ROS levels by 1.4- and 1.6-fold in Panc-1 and MIA PaCa-2 cells, respectively
ECAR↓, EGCG affected glycolysis by suppressing the extracellular acidification rate through the reduction of the activity and levels of the glycolytic enzymes phosphofructokinase and pyruvate kinase.
ChemoSen↑, EGCG sensitized gemcitabine to inhibit pancreatic cancer cell growth in vitro and in vivo.
selectivity↑, EGCG at 80 µM for 72 h had significantly less effect on the HPNE cells, reducing cell growth by only 24%
Glycolysis↓, EGCG Inhibits Glycolysis through Suppressing Rate-Limiting Enzymes. EGCG Plus Gemcitabine Further Inhibits Glycolysis
PFK↓, EGCG treatment reduced both the activity and expression levels of phosphofructokinase (PFK) and pyruvate kinase (PK) in Panc-1 and MIA PaCa-2 cells
PKA↓,
HK2∅, EGCG failed to reduce hexokinases II (HK2) and lactate dehydrogenase A (LDHA) protein expression levels
LDHA∅,
PFKP↓, EGCG reduced the levels of PFKP and PKM2 (p < 0.01 for both) in pancreatic tumor xenograft homogenates, obtained from mice treated with EGCG
PKM2↓,
H2O2↑, EGCG at 40 µM increased H2O2 levels by 1.5- and 1.9-fold in Panc-1 and MIA PaCa-2 cells
TumW↓, EGCG and gemcitabine, given as single agents, reduced tumor weight by 40% and 52%, respectively, compared to vehicle-treated controls (p < 0.05 and p < 0.01). In combination, EGCG plus gemcitabine reduced tumor weight by 67%,

2310- EGCG,    Epigallocatechin-3-gallate downregulates PDHA1 interfering the metabolic pathways in human herpesvirus 8 harboring primary effusion lymphoma cells
- in-vitro, lymphoma, PEL
GLUT3↑, EGCG increased GLUT3 and decreased PDHA1 and GDH1 expression to disrupt glycolysis and glutaminolysis in PEL cells
PDHA1↓,
GDH↓,
ROS↑, Previously we have demonstrated that EGCG induces ROS generation and cell death in HHV8 harboring PEL cells
Glycolysis↓, EGCG induced PEL cell death may due to suppresses both the aerobic glycolysis and oxidative phosphorylation
OXPHOS↓,

2459- EGCG,    Epigallocatechin gallate inhibits human tongue carcinoma cells via HK2‑mediated glycolysis
- in-vitro, Tong, Tca8113 - in-vitro, Tong, TSCCa
EGFR↓, EGCG exposure substantially decreased EGF-induced EGF receptor (EGFR), Akt and ERK1/2 activation, as well as the downregulation of hexokinase 2 (HK2).
Akt↓,
ERK↓,
HK2↓,
GlucoseCon↓, EGCG dose-dependently inhibited the consumption of glucose (Fig. 2A and B, middle) and production of lactate
lactateProd↓,
Glycolysis↓, EGCG downregulates HK2 expression and decreases human tongue carcinoma cell glycolysis.

2422- EMD,    Anti-Cancer Effects of Emodin on HepG2 Cells as Revealed by 1H NMR Based Metabolic Profiling
- in-vitro, HCC, HepG2
HK2↓, The mRNA levels of hexokinase II (HKII), pyruvate kinase isoform M2 (PKM2) and lactate 19 dehydrogenase-A (LDHA) in emodin treated cells were all decreased in a concentration-dependent manner
PKM2↓,
LDHA↓,
Glycolysis↓, levels of glycolysis related proteins were significantly decreased. emodin indeed inhibited glycolysis of HepG2 cells.
TumCCA↑, induced cell cycle arrest, apoptosis and ROS generation
ROS↓,
glut↓, level of glutamine was decreased after emodin treatment
Hif1a↓, generation of ROS induces decreased expression of HIF-1

988- EMD,    Emodin Induced Necroptosis and Inhibited Glycolysis in the Renal Cancer Cells by Enhancing ROS
- in-vitro, RCC, NA
Necroptosis↑, emodin induces necroptosis, but not apoptosis, in renal cancer cells
p‑RIP1↑,
MLKL↑,
ROS↑, levels of ROS increased upon emodin treatment in a dose-dependent manner
Glycolysis↓,
GLUT1↓,
PI3K↓,
Akt↓,

1654- FA,    Molecular mechanism of ferulic acid and its derivatives in tumor progression
- Review, Var, NA
AntiCan↑, FA has anti-inflammatory, analgesic, anti-radiation, and immune-enhancing effects and also shows anticancer activity,
Inflam↓,
RadioS↑,
ROS↑, FA can cause mitochondrial apoptosis by inducing the generation of intracellular reactive oxygen species (ROS)
Apoptosis↑,
TumCCA↑, G0/G1 phase
TumCMig↑, inducing autophagy; inhibiting cell migration, invasion, and angiogenesis
TumCI↓,
angioG↓,
ChemoSen↑, synergistically improving the efficacy of chemotherapy drugs and reducing adverse reactions.
ChemoSideEff↓,
P53↑, FA could increase the expression level of p53 in MIA PaCa-2 pancreatic cancer cells
cycD1/CCND1↓, while reducing the expression levels of cyclin D1 and cyclin-dependent kinase (CDK) 4/6.
CDK4↓,
CDK6↓,
TumW↓, FA treatment was found to reduce tumor weight in a dose-dependent manner, increase miR-34a expression, downregulate Bcl-2 protein expression, and upregulate caspase-3 protein expression
miR-34a↑,
Bcl-2↓,
Casp3↑,
BAX↑,
β-catenin/ZEB1↓, isoferulic acid dose-dependently downregulated the expression of β-catenin and MYC proto-oncogene (c-Myc), inducing apoptosis
cMyc↓,
Bax:Bcl2↑, FXS-3 can inhibit the activity of A549 cells by upregulating the Bax/Bcl-2 ratio
SOD↓, After treatment with FA, Cao et al. [40] observed an increase in ROS production and a decrease in superoxide dismutase activity and glutathione content in EC-1 and TE-4 oesophageal cancer cells
GSH↓,
LDH↓, FA could promote the release of lactate dehydrogenase (LDH)
ERK↑, A can activate the ERK1/2 pathway
eff↑, conjugated zinc oxide nanoparticles with FA (ZnONPs-FA) to act on hepatoma Huh-7 and HepG2 cells. The results showed that ZnONPs-FA could induce oxidative DNA damage and apoptosis by inducing ROS production.
JAK2↓, by inhibiting the JAK2/STAT6 immune signaling pathway
STAT6↓,
NF-kB↓, thus inhibiting the activation of NF-κB
PYCR1↓, FA can target PYCR1 and inhibit its enzyme activity in a concentration-dependent manner.
PI3K↓, FA inhibits the activation of the PI3K/AKT pathway
Akt↓,
mTOR↓, FA could significantly reduce the expression level of mTOR mRNA and Ki-67 protein in A549 lung cancer graft tissue
Ki-67↓,
VEGF↓,
FGFR1↓, FA is a novel FGFR1 inhibitor
EMT↓, FA can inhibit EMT
CAIX↓, selectively inhibit CAIX
LC3II↑, Autophagy vacuoles and increased LC3-II and p62 autophagy proteins were observed after treatment with this compound
p62↑,
PKM2↓, FA could inhibit the expression of PKM2 and block aerobic glycolysis
Glycolysis↓,
*BioAv↓, FA has poor solubility in water and a poor ability to pass through biological barriers [118]; therefore, the extent to which it is metabolized in vivo after oral administration is largely unknown

2494- Fenb,    Oral Fenbendazole for Cancer Therapy in Humans and Animals
- Review, Var, NA
Glycolysis↓, fenbendazole and its promising anticancer biological activities, such as inhibiting glycolysis, down-regulating glucose uptake, inducing oxidative stress, and enhancing apoptosis in published experimental studies.
GlucoseCon↓,
ROS↑,
Apoptosis↑,
BioAv↓, Due to its poor absorption by oral administration, fenbendazole is particularly effective for targeting intestinal parasites
eff↑, Tippens began self-administering 222 mg fenbendazole orally, along with vitamin E supplements, CBD oil, and bioavailable curcumin. After three months of self-administration, a PET scan revealed no detectable cancer cells in his body.
toxicity↓, In rodents, its lethal dose (LD50) exceeded 10 g/kg, which is 1,000 times the therapeutic level
BioAv↑, vehicles for increasing the bioavailability of oral fenbendazole, it would be worthwhile to focus on dimethyl sulfoxide (DMSO), Salicylic acid, and methyl-β-cyclodextrin.
BioAv↑, Another method to improve the solubility of fenbendazole would be to complex it with methyl-β-cyclodextrin at a 1:1 ratio.
hepatoP↓, In both cases, despite the hepatotoxicity, patients’ liver function recovered rapidly upon discontinuing fenbendazole.
eff↑, combining fenbendazole with glycolysis inhibitors and hepatoprotective pharmaceutical or nutraceutical agents can lead to synergic therapeutic activity while reducing potential liver toxicity.

2313- Flav,    Flavonoids against the Warburg phenotype—concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism
- Review, Var, NA
Warburg↓, Flavonoids modulate key pathways involved in the Warburg phenotype including but not limited to PKM2, HK2, GLUT1 and HIF-1.
antiOx↑, Flavonoids represent a diverse group of phytochemicals (Fig. 3) that exhibit antioxidative, antiangiogenic and overall antineoplastic efficacy
angioG↓,
Glycolysis↓, Apigenin (AP) blocked glycolysis through regulation of PKM2 activity and expression in a colon cancer cell line (HCT116)
PKM2↓,
PKM2:PKM1↓, AP is regarded as a potential allosteric inhibitor of PKM2. AP could maintain a low PKM2/PKM1 ratio as a consequence of inhibition of the β-catenin/c-Myc/PTBP1 pathway
β-catenin/ZEB1↓,
cMyc↓,
HK2↓, QUE reduced the level of HK2 and suppressed Akt/mTOR signalling in hepatocellular cancer lines (SMMG-7721, BEL-7402) in vitro.
Akt↓,
mTOR↓,
GLUT1↓, EGCG demonstrated anticancer efficacy against 4T1 via reduction of GLUT1 expression
Hif1a↓, BA suppressed glycolysis via PTEN/Akt/HIF-1α, it is a possible therapeutic sensitiser against gastric cancer

5206- Gallo,    Galloflavin prevents the binding of lactate dehydrogenase A to single stranded DNA and inhibits RNA synthesis in cultured cells
- in-vitro, Var, NA
LDHA↓, Novel LDH-A inhibitors which hinder aerobic glycolysis of cancer cells
Glycolysis↓,
TumCP↓, inhibitors which bind the NADH site can exert their antiproliferative activity not only by blocking aerobic glycolysis but also by causing an inhibition of RNA synthesis tumcp

5205- Gallo,    Evaluation of the anti-tumor effects of lactate dehydrogenase inhibitor galloflavin in endometrial cancer cells
- in-vitro, Endo, ISH
LDH↓, novel lactate dehydrogenase (LDH) inhibitor, Galloflavin, as a therapeutic agent for endometrial cancer.
TumCG↓, Galloflavin effectively inhibited cell growth in endometrial cancer cell lines and primary cultures of human endometrial cancer
LDHA↓, GF significantly reduced LDHA activity
Apoptosis↑, GF was responsible for the activation of the mitochondrial apoptosis pathway, accompanied by an increase in cleaved caspase3 and a decrease in MCL-1 and BCL-2 protein
cl‑Casp3↑,
Mcl-1↓,
Bcl-2↓,
TumCCA↑, GF induces cell cycle changes by altering different checkpoints in different endometrial cancer cells
ROS↑, GF was also shown to increase reactive oxygen species (ROS) and mitochondrial DNA damage after 24 hours
mt-DNAdam↑,
GlucoseCon↓, Inhibition of LDHA activity by GF resulted in a decreased rate of glucose uptake and ATP production
ATP↓,
PDH↑, with subsequent increased pyruvate dehydrogenase (PDH) protein expression and production of pyruvate
Pyruv↑,
Glycolysis↓, direct effect of GF on the glucose metabolism by impairing cytosolic glycolysis in the endometrial cancer cells
TCA↑, GF increased glutaminase protein expression, and enhanced Krebs cycle activity, by increasing the production of malate,
cMyc↓, GF decreased c-Myc expression in a dose-dependent manner after 24 hours of treatment.
E-cadherin↑, E–cadherin increased while Slug proteins decreased after treatment with GF (
Slug↓,

935- Gallo,    Galloflavin, a new lactate dehydrogenase inhibitor, induces the death of human breast cancer cells with different glycolytic attitude by affecting distinct signaling pathways
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
LDH↓, our experimental data show that the inhibition of LDH caused by GF can exert comparable growth inhibitory effects on breast cancer cells
ROS↑, induction of an oxidative stress condition
TumCP↓, Galloflavin (GF), a recently identified lactate dehydrogenase inhibitor, hinders the proliferation of cancer cells by blocking glycolysis and ATP production.
Glycolysis↓,
ATP↓,
ER-α36↓, In MCF-7 cells we observed a down regulation of the ERα-mediated signaling needed for cell survival
Apoptosis?, mechanism of cell death was found to be apoptosis induction

934- Gallo,    Galloflavin (CAS 568-80-9): a novel inhibitor of lactate dehydrogenase
- Analysis, NA, NA
LDH↓, hinders both the A and B isoforms of the enzyme.
Glycolysis↓, galloflavin blocked aerobic glycolysis at micromolar concentrations
Apoptosis↑,

2512- H2,    Hydrogen Attenuates Allergic Inflammation by Reversing Energy Metabolic Pathway Switch
- in-vivo, asthmatic, NA
selectivity↑, we treated mice with HRS for 7 days. HRS had no effects on OXPHOS and glycolytic activities in control mice
lactateProd↓, but prevented the elevation in lactate and reduction in ATP production in lungs of OVA-sensitized and challenged mice
ATP↑,
HK2↓, Consistently, HRS attenuated the increase in HK and PFK activities
PFK↓,
Hif1a↓, OVA sensitization and challenge increased HIF-1α nuclear translocation (stimulated HIF-1α activity), which was inhibited by HRS treatment
PGC-1α↑, By contrast, OVA sensitization and challenge downregulated PGC-1α protein expression, and HRS treatment reversed this downregulation
Glycolysis↓, H2 reverses energy metabolic switch by inhibiting glycolytic enzyme activities and by stimulating mitochondrial OXPHOS enzyme activities
OXPHOS↑,
Dose↝, HRS was prepared by dipping a plastic-shelled stick consisting of metallic magnesium (99.9% pure) and natural stones (Doctor SUISOSUI, Friendear Inc., Tokyo, Japan) into sterilized saline.

2400- HCAs,    The Mixture of Ferulic Acid and P-Coumaric Acid Suppresses Colorectal Cancer through lncRNA 495810/PKM2 Mediated Aerobic Glycolysis
- in-vitro, CRC, NA - in-vivo, CRC, NA
PKM2↓, FA + p-CA remodel aerobic glycolysis by inhibiting the glycolysis-associated lncRNA 495810 and the glycolytic rate-limiting enzyme M2 type pyruvate kinase (PKM2)
Glycolysis↓, FA + p-CA obstruct the aerobic glycolysis of colorectal cancer cells via the lncRNA 495810/PKM2 axis, which provides a nutrition intervention and treatment candidate for colorectal cancer.
TumCG↓, results showed that FA + p-CA restrained the growth of tumors in AOM/DSS CRC mice

2071- HNK,    Identification of senescence rejuvenation mechanism of Magnolia officinalis extract including honokiol as a core ingredient
- Review, Nor, HaCaT
*ROS↓, Magnolia officinalis (M. officinalis) extract significantly lowered the levels of ROS in senescent fibroblasts.
*antiOx↑, honokiol was demonstrated as a core ingredient of M. officinalis extract that exhibits antioxidant effects.
*AntiAge↑, new approaches to anti–aging treatments
*MMP↑, increases MMP
*ECAR↓, senescent fibroblasts treated with M. officinalis extract had lower ECAR values than those treated with DMSO, suggesting that M. officinalis treatment lowed glycolysis rate
*Glycolysis↓, honokiol, similar to M. officinalis, reduced the dependence of glycolysis as an energy source, indicating restoration of mitochondrial function by honokiol.
*PAR-2↓, downregulation of PAR–2 expression by M. officinalis may reduce skin pigmentation.
*CXCL12↑, upregulation of SDF–1 expression by M. officinalis may reduce skin pigmentation.
*BMAL1↑, activation of Bmal–1 expression by M. officinalis promote skin turnover.
*mt-ROS↓, compared to M. officinalis extract, honokiol at 1 and 10 μM was more effective in lowering mitochondrial ROS levels
*OXPHOS↓, Inhibition of oxidative phosphorylation and induction of a compensatory shift toward glycolysis resulted in lower compensatory glycolysis in honokiol–treated senescent fibroblasts

960- HNK,    Honokiol Inhibits HIF-1α-Mediated Glycolysis to Halt Breast Cancer Growth
- vitro+vivo, BC, MCF-7 - vitro+vivo, BC, MDA-MB-231
OCR↑, which resulted in an increase in OCR and a decrease in ECAR, glucose uptake, lactic acid production and ATP production.
ECAR↓,
GlucoseCon↓, decreased glucose uptake, lactate production and ATP production in cancer cells.
lactateProd↓,
ATP↓,
Glycolysis↓,
Hif1a↓,
GLUT1↓,
HK2↓,
PDK1↓,
Apoptosis↑,
LDHA↓, upregulation of LDHA mediated by HIF-1α promoted the formation of lactic acid from pyruvate, which contributed to the acidification of the tumor microenvironment. Our experimental observation results showed that these changes were reversed by HNK

2887- HNK,    Honokiol Restores Microglial Phagocytosis by Reversing Metabolic Reprogramming
- in-vitro, AD, BV2
*Glycolysis↑, switch from oxidative phosphorylation to anaerobic glycolysis and enhancing ATP production.
*ATP↑,
*ROS↓, honokiol reduced mitochondrial reactive oxygen species production and elevated mitochondrial membrane potential.
*MMP↑,
*OXPHOS↑, Honokiol enhanced ATP production by promoting mitochondrial OXPHOS in BV2 cell
*PPARα↑, Therefore, we argue that honokiol increases the expression of PPAR and PGC1, thus regulating a metabolic switch from glycolysis to OXPHOS
*PGC-1α↑,

2178- itraC,    Itraconazole inhibits tumor growth via CEBPB-mediated glycolysis in colorectal cancer
- in-vivo, CRC, HCT116
TumCG↓, We found that itraconazole could inhibit tumor growth and glycolysis
Glycolysis↓, itraconazole could repress CRC tumor growth by inhibiting glycolysis
CEBPB?, CEBPB was a new target for itraconazole, and that silencing CEBPB could repress CRC glycolysis and tumor growth by inhibiting ENO1 expression
ENO1↓, glycolysis enzymes (ENO1, LDHA, PGK1, PKM and GAPDH) was significantly decreased after itraconazole treatment
LDHA↓,
PKM2↓,
GAPDH↓,
ECAR↓, itraconazole treatment could significantly reduce ECAR and OCR
OCR↓,

1070- IVM,    Ivermectin accelerates autophagic death of glioma cells by inhibiting glycolysis through blocking GLUT4 mediated JAK/STAT signaling pathway activation
- vitro+vivo, GBM, NA
TumCG↓,
LC3II↑,
p62↓,
ATP↓,
Pyruv↓,
GlucoseCon↑, promoted glucose uptake
HK2↓,
PFK1↓,
GLUT4↓,
Glycolysis↓,
JAK2↓,
p‑STAT3↓,
p‑STAT5↓,

2390- KaempF,    Kaempferol Can Reverse the 5-Fu Resistance of Colorectal Cancer Cells by Inhibiting PKM2-Mediated Glycolysis
- in-vitro, CRC, HCT8
eff↑, kaempferol could reverse the drug resistance of HCT8-R cells to 5-Fu, suggesting that kaempferol alone or in combination with 5-Fu has the potential to treat colorectal cancer
GlucoseCon↓, kaempferol treatment significantly reduced glucose uptake and lactic acid production in drug-resistant colorectal cancer cells.
lactateProd↓,
PKM2↓, kaempferol promotes the expression of microRNA-326 (miR-326) in colon cancer cells, and miR-326 could inhibit the process of glycolysis by directly targeting pyruvate kinase M2 isoform (PKM2) 3′-UTR (untranslated region) to inhibit PKM2
Glycolysis↓, Kaempferol Promotes 5-Fu Sensitivity by Inhibiting Glycolysis
glucose↑, kaempferol treatment dramatically increased the content of glucose in HCT8-R cell culture medium (Figure 3E) and decreased the content of lactate (Figure 3F), suggesting that kaempferol might promote the 5-Fu sensitivity by inhibiting glycolysis.

2351- lamb,    Anti-Warburg effect via generation of ROS and inhibition of PKM2/β-catenin mediates apoptosis of lambertianic acid in prostate cancer cells
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3
proCasp3↓, LA exerted cytotoxicity, increased sub G1 population and attenuated the expression of pro-Caspase3 and pro-poly (ADP-ribose) polymerase (pro-PARP) in DU145 and PC3 cells
proPARP↓,
LDHA↓, LA reduced the expression of lactate dehydrogenase A (LDHA), glycolytic enzymes such as hexokinase 2 and pyruvate kinase M2 (PKM2) with reduced production of lactate in DU145 and PC3 cells
Glycolysis↓,
HK2↓,
PKM2↓,
lactateProd↓,
p‑STAT3↓, inhibited the expression of p-STAT3, cyclin D1, C-Myc, β-catenin, and p-GSK3β with the decrease of nuclear translocation of p-PKM2
cycD1/CCND1↓,
cMyc↓,
β-catenin/ZEB1↓,
p‑GSK‐3β↓,
ROS↑, LA generated ROS in DU145 and PC3
eff↓, while ROS scavenger NAC (N-acetyl L-cysteine) blocked the ability of LA to reduce p-PKM2, PKM2, β-catenin, LDHA, and pro-caspase3 in DU145 cells.

2453- LE,    The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors
- Review, Var, NA
HK2↓, Therefore, it can be concluded that GA can inhibit HK II through the PI3K/AKT pathway, thus inhibiting the proliferation and glycolysis metabolism of LC cells [160]
PI3K↓,
Akt↓,
TumCP↓,
Glycolysis↓,

986- LT,  doxoR,    Luteolin as a glycolysis inhibitor offers superior efficacy and lesser toxicity of doxorubicin in breast cancer cells
- in-vitro, BC, 4T1 - in-vitro, BC, MCF-7
SOD↓, the activity of SOD and CAT was increased in serum and was decreased in tumor by Lu in vivo
Catalase↓,
Glycolysis↓, glycolytic inhibitor

2929- LT,    Loss of BRCA1 in the cells of origin of ovarian cancer induces glycolysis: A window of opportunity for ovarian cancer chemoprevention
- in-vitro, Ovarian, NA
HK2↓, . Figure 5b Aspirin and luteolin suppress HK2 and glycolysis in IOSE and FT cells.
Myc↓, Two agents, aspirin and luteolin, induced a dose-dependent decrease in the protein levels of HK2 and reduced MYC expression
Glycolysis↓,

3276- Lyco,    Lycopene modulates cellular proliferation, glycolysis and hepatic ultrastructure during hepatocellular carcinoma
- in-vivo, HCC, NA
G6PD↓, Moreover, NDEA treatment caused a significant increase in liver G6PD activity in the NDEA group when compared to the control and LycT groups.
PCNA↓, The LycT + NDEA group showed a significant decrease in mRNA expression of PCNA and Cyclin D1 when compared to the NDEA group
cycD1/CCND1↓,
P21↑, A significant increase in the expression of p21 was observed in the LycT + NDEA group when compared to the contro
Hif1a↓, Pre-treatment with LycT in NDEA-challenged mice resulted in a significant reduction in the expression of HIF-1α at week 24 when compared to the NDEA group
Glycolysis↓, Moreover, significant reductions in the activities of glycolytic enzymes following LycT pre-treatment in NDEA-challenged mice were inversely related to HCC development.

2545- M-Blu,    Reversing the Warburg Effect as a Treatment for Glioblastoma
- in-vitro, GBM, U87MG - NA, AD, NA - in-vitro, GBM, A172 - in-vitro, GBM, T98G
Warburg↓, Here, we documented that methylene blue (MB) reverses the Warburg effect evidenced by the increasing of oxygen consumption and reduction of lactate production in GBM cell lines
OCR↑, increases cellular oxygen consumption, and decreases lactate production in murine hippocampal cells
lactateProd↓,
TumCP↓, MB decreases GBM cell proliferation and halts the cell cycle in S phase.
TumCCA↑,
AMPK↑, Through activation of AMP-activated protein kinase, MB inactivates downstream acetyl-CoA carboxylase and decreases cyclin expression.
ACC↓,
Cyc↓,
neuroP↑, There is mounting evidence that MB enhances brain metabolism and exerts neuroprotective effects in multiple neurodegenerative disease models including Parkinson, Alzheimer, and Huntington disease
Cyt‑c↝, MB has long been known as an electron carrier, which is best represented by MB ability to increase the rate of cytochrome c reduction in isolated mitochondria
Glycolysis↓, MB Decreases Aerobic Glycolysis in U87 Cells
ECAR↓, MB increases OCR and decreases ECAR in U87 cells
TumCG↓, MB Inhibits Tumor Growth in Vitro
other↓, MB dramatically inhibits expression of cyclin A2, B1,and D1 while having less effect on cyclin E1

2542- M-Blu,    In Vitro Methylene Blue and Carboplatin Combination Triggers Ovarian Cancer Cells Death
- in-vitro, Ovarian, OV1369 - in-vitro, Ovarian, OV1946 - in-vitro, Nor, ARPE-19
BioAv↝, our study reveals MB’s distinct cellular uptake, with ARPE-19 absorbing 5 to 7 times more MB than OV1946 and OV1369-R2.
TumCP↓, Treatment with 50 µM MB (MB-50) effectively curtailed the proliferation of both ovarian cancer cell lines.
GlutaM↓, MB-50 exhibited the ability to quell glutaminolysis and the Warburg effect in cancer cell cultures.
Warburg↓,
OCR↑, MB-50 spurred oxygen consumption, disrupted glycolytic pathways, and induced ATP depletion in the chemo-sensitive OV1946 cell line.
Glycolysis↓,
ATP↓,
BioAv↝, The reduced permeability of cancer cell membranes, including mitochondria, suggests limited internalization of MB into their cytoplasm or mitochondria, consistent with their preference for aerobic glycolysis, a hallmark of the Warburg effect.
ROS↑, Consistent with our findings, they reported a decrease in intracellular ATP levels, which, in turn, led to increased generation of reactive oxygen species (ROS)

2541- M-Blu,    Spectroscopic Study of Methylene Blue Interaction with Coenzymes and its Effect on Tumor Metabolism
- in-vivo, Var, NA
TumCG↓, In the group receiving MB with drinking water, a decrease of the tumor growth rate, reduction of oxygenation level, and a1/a2 metabolic index were observed, which confirms the shift from glycolysis to oxidative phosphorylation.
Glycolysis↓,
OXPHOS↑,
ROS↑, The ability of MB to generate reactive oxygen species together with a small molecular size makes this dye attractive for using it as a photosensitizer in photodynamic therapy
OCR↑, MB can increase oxygen consumption, decrease glycolysis and increase glucose uptake in vitro
GlucoseCon↑,
lactateProd↓, The decrease of the lactate amount and extracellular acidification rate after MB introduction, which is reported in the literature [31], is supposed to be a secondary effect mediated by the metabolic shift towards oxidation phosphorylation as a resul

2540- M-Blu,    Alternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dots
- Review, Var, NA - Review, AD, NA
*OCR↑, MB was found to increase oxygen consumption of normal tissues having aerobic glycolysis and of tumors
*Glycolysis↓, Methylene blue increases oxygen consumption, decrease glycolysis, and increases glucose uptake in vitro.
*GlucoseCon↑, Methylene blue enhances glucose uptake and regional cerebral blood flow in rats upon acute treatment.
neuroP↑, methylene blue provides protective effect in neuron and astrocyte against various insults in vitro and in rodent models of Alzheimer’s, Parkinson’s, and Huntington’s disease.
Warburg↓, In glioblastoma cells, methylene blue reverses Warburg effect by enhancing mitochondrial oxidative phosphorylation, arrests glioma cell cycle at s-phase, and inhibits glioma cell proliferation.
mt-OXPHOS↑,
TumCCA↑,
TumCP↓,
ROS⇅, MB has very unique redox property that exists in equilibrium between oxidized state in dark blue (MB) and colorless reduced state (leucomethylene blue), making it both prooxidant and antioxidant under different conditions.
*cognitive↑, Methylene blue feeding improved water-maze and bridge walking performance in 5 X FAD mice. MB enhances memory function in normal rodents potentially through neurometabolic mechanisms
*mTOR↓, MB has been demonstrated to induce autophagy and attenuate tauopathy through inhibition of mTOR signaling both in vitro and in vivo
*mt-antiOx↑, Secondly, the distinct redox property enables MB as a regenerable anti-oxidant in mitochondria that distinct from the traditional free radical scavenges
*memory↑, , MB has been found to improve various experimental memory tasks in rodents
*BBB↑, MB can cross BBB and reach brain at concentrations 10 times higher than that in the circulation
*eff↝, In fibroblast cells, MB has been shown to stimulate 2-deoxyglucose uptake (Louters et al., 2006; Roelofs et al., 2006). Using MRI and PET, we demonstrated that acute treatment of MB significantly enhance glucose uptake
*ECAR↓, MB increased oxygen consumption rate and decreased extracellular acidification rate in both neuronal cells and astrocytes
eff↑, MB has also been used as a tracer for cancer diagnosis and as a photosensitizer for cancer treatment
lactateProd↓, MB increase oxygen consumption rate, decrease lactic acid production and extracellular acidification rate, reduce NADPH, and inhibit proliferation
NADPH↓,
OXPHOS↑, increases oxidative phosphorylation, decreases glycolytic flux and metabolic intermediates, hence, exhausts the building brick for cancer cell proliferation.
AMPK↑, MB is capable of activating AMPK signal pathway
selectivity↑, with low toxicity, and the high affinity to both neuronal and cancer tissues

995- MEL,    Melatonin Treatment Triggers Metabolic and Intracellular pH Imbalance in Glioblastoma
- vitro+vivo, GBM, NA
LDHA↓,
MCT4↓,
lactateProd↓,
i-pH↓, decrease in intracellular pH: melatonin treatment induced a pH reversal with intracellular acidosis parallel to a downregulation in glycolysis in GBM.
ROS↑,
ATP↓,
TumCD↑, cytotoxic effects on GBM were due, at least in part, to intracellular pH modulation
TumCCA↑, cell cycle arrest at G0/G1 in both GBM1A and QNS120 and G2/M in GBM1A
PDH↓, decrease in pyruvate dehydrogenase (PDH) expression for both cell lines at aMT 3.0 mM
Glycolysis↓,
GlucoseCon↓,
TumCG↓, in vivo

994- MET,    Tumor metabolism destruction via metformin-based glycolysis inhibition and glucose oxidase-mediated glucose deprivation for enhanced cancer therapy
- in-vitro, Var, NA
Glycolysis↓,
HK2↓,
ATP↓,
AMPK↑,
P53↑,
Warburg↓,
Apoptosis↑,

2374- MET,    Metformin Induces Apoptosis and Downregulates Pyruvate Kinase M2 in Breast Cancer Cells Only When Grown in Nutrient-Poor Conditions
- in-vitro, BC, MCF-7 - in-vitro, BC, SkBr3 - in-vitro, BC, MDA-MB-231
eff↑, reduction of nutrient supply in tumors can increase metformin efficacy and that modulation of PKM2 expression/activity could be a promising strategy to boost metformin anti-cancer effect.
Apoptosis↑,
Glycolysis↓, Finally, we showed that, in nutrient-poor conditions, metformin was able to modulate the intracellular glycolytic equilibrium by downregulating PKM2 expression
PKM2↓,
mTOR↓, Glucose availability influences metformin effect on apoptosis without affecting its ability to downregulate the mTOR pathway
PARP↓, metformin ability to induce PARP inactivation

2384- MET,    Integration of metabolomics and transcriptomics reveals metformin suppresses thyroid cancer progression via inhibiting glycolysis and restraining DNA replication
- in-vitro, Thyroid, BCPAP - in-vivo, NA, NA - in-vitro, Thyroid, TPC-1
Glycolysis↓, Metformin promotes the metabolic transition from glycolysis to oxidative phosphorylation.
OXPHOS↑,
tumCV↓, metformin reduced cell viability, invasion, migration, and EMT, and induced apoptosis and cell cycle G1 phase arrest in thyroid cancer.
TumCI↓,
TumCMig↓,
EMT↓,
Apoptosis↑,
TumCCA↑, cell cycle G1 phase
LDHA↓, metformin suppressed glycolysis by downregulating the key glycolytic enzymes LDHA and PKM2 and upregulating IDH1 expression in thyroid cancer.
PKM2↓,
IDH1↑,
TumCG↓, Metformin inhibits the growth of thyroid cancer in vivo

2249- MF,    Pulsed electromagnetic fields modulate energy metabolism during wound healing process: an in vitro model study
- in-vitro, Nor, L929
*TumCMig↑, PEMFs with specific parameter (4mT, 80 Hz) promoted cell migration and viability.
*tumCV↑,
*Glycolysis↑, PEMFs-exposed L929 cells was highly glycolytic for energy generation
*ROS↓, PEMFs enhanced intracellular acidification and maintained low level of intracellular ROS in L929 cells.
*mitResp↓, shifting from mitochondrial respiration to glycolysis
*other↝, Furthermore, the analysis of ECAR/ OCR basal ratio demonstrated a tendency toward to glycolytic phenotype in L929 cells under PEMF exposure, compared to control group
*OXPHOS↓, PEMFs promoted the transformation of energy metabolism pattern from oxidative phosphorylation to aerobic glycolysis
*pH↑, result of pH detection by flow cytometer indicated the pH level in L929 cells was significantly increased in the PEMFs group compared to the control group
*antiOx↑, PEMFs upregulated the expression of antioxidant or glycolysis related genes
*PFKM↑, Pfkm, Pfkl, Pfkp, Pkm2, Hk2, Glut1, were also significantly up-regulated in the PEMFs group
*PFKL↑,
*PKM2↑,
*HK2↑,
*GLUT1↑,
*GPx1↑, GPX1, GPX4 and Sod 1 expression were significantly higher in the PEMFs group compared to the control group
*GPx4↑,
*SOD1↑,

2247- MF,    Effects of Pulsed Electromagnetic Field Treatment on Skeletal Muscle Tissue Recovery in a Rat Model of Collagenase-Induced Tendinopathy: Results from a Proteome Analysis
- in-vivo, Nor, NA
*Glycolysis↓, PEMF-treated animals exhibited decreased glycolysis and increased LDHB expression, enhancing NAD signaling and ATP production
*LDHB↑,
*NAD↑,
*ATP↑,
*antiOx↑, Antioxidant protein levels increased, controlling ROS production.
*ROS↑,
*YAP/TEAD↑, upregulation of YAP and PGC1alpha and increasing slow myosin isoforms, thus speeding up physiological recovery.
*PGC-1α↑,
*TCA↑, increased in PEMF-treated injured limbs
*FAO↑,
*OXPHOS↑, Oxidative phosphorylation was increased in the muscle of injured rats that underwent PEMF treatment

2245- MF,    Quantum based effects of therapeutic nuclear magnetic resonance persistently reduce glycolysis
- in-vitro, Nor, NIH-3T3
Warburg↓, tNMR might have the potential to counteract the Warburg effect known from many cancer cells which are prone to glycolysis even under aerobic conditions.
Hif1a↓, combined treatment of tNMR and hypoxia (tNMR hypoxia) led to significantly altered HIF-1α protein levels, namely a further overall reduction in protein amounts
*Hif1a∅, Under normoxic conditions we did not find significant differences in Hif-1α mRNA and protein expression
Glycolysis↓, hypoxic tNMR treatment, driving cellular metabolism to a reduced glycolysis while mitochondrial respiration is kept constant even during reoxygenation.
*lactateProd↓, tNMR reduces lactate production and decreases cellular ADP levels under normoxic conditions
*ADP:ATP↓,
Pyruv↓, Intracellular pyruvate, which was as well decreased in hypoxic control cells, appeared to be further decreased after tNMR under hypoxia
ADP:ATP↓, tNMR under hypoxia further decreased the hypoxia induced decrease of the intracellular ADP/ATP ratio
*PPP↓, pentose phosphate pathway (PPP) is throttled after tNMR treatment, while cell proliferation is enhanced
*mt-ROS↑, tNMR under hypoxia increases mitochondrial and extracellular, but reduces cytosolic ROS
*ROS↓, but reduces cytosolic ROS
RPM↑, Because EMFs are known to affect ROS levels via the radical pair mechanism (RPM)
*ECAR↓, tNMR under normoxic conditions reduces the extracellular acidification rate (ECAR)

2244- MF,    Little strokes fell big oaks: The use of weak magnetic fields and reactive oxygen species to fight cancer
- Review, Var, NA
RPM↑, WEMFs affect multiple cellular processes through mechanisms such as the radical pair mechanism (RPM), which alters reactive oxygen species (ROS) levels, mitochondrial function, and glycolysis
Glycolysis∅, WEMF parallel to the magnetic field (does not enchance glycolysis)
ROS↑, WEMF can augment this effect by enhancing mitochondrial respiration, which increases ROS levels within cancer cells. This augmentation makes cancer cells more susceptible to treatment by promoting oxidative stress that can lead to apoptosis
ChemoSen↑, Chemotherapeutic agents, such as doxorubicin, primarily exert their effects by generating ROS to induce cell death. WEMF can augment this effect by enhancing mitochondrial respiration, which increases ROS levels
RadioS↑, Similarly, WEMF can enhance the efficacy of radiation therapy by increasing ROS production and sensitizing cancer cells to radiation-induced DNA damage
selectivity↑, primary advantage of WEMF is its non-invasive, non-ionizing nature, which minimizes collateral damage to healthy tissue.

2260- MF,    Alternative magnetic field exposure suppresses tumor growth via metabolic reprogramming
- in-vitro, GBM, U87MG - in-vitro, GBM, LN229 - in-vivo, NA, NA
TumCP↓, proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz.
TumCG↓, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival
OS↑,
ROS↑, This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression.
SOD2↑,
eff↓, anti-cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger.
ECAR↓, decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR).
OCR↑,
selectivity↑, This suggests that AMF-induced metabolic reprogramming occurs in GBM cells but not in normal cells. Furthermore, in cancer cells, AMF decreased ECAR and increased OCR, while there were no changes in normal cells.
*toxicity∅, did not affect non-cancerous human cells [normal human astrocyte (NHA), human cardiac fibroblast (HCF), human umbilical vein endothelial cells (HUVEC)].
TumVol↓, The results showed a significant treatment effect, as assessed by tumor volume, after conducting AMF treatment five times a week for 2 weeks
PGC-1α↑, Corresponding to the rise in ROS, there was also a time-dependent increase in PGC1α protein expression post-AMF exposure
OXPHOS↑, enhancing mitochondrial oxidative phosphorylation (OXPHOS), leading to increased ROS production
Glycolysis↓, metabolic mode of cancer cells to shift from glycolysis, characteristic of cancer cells, toward OXPHOS, which is more typical of normal cells.
PKM2↓, We extracted proteins that changed commonly in U87 and LN229 cells. Among the individual proteins related to metabolism, pyruvate kinase M2 (PKM2) was found to be inhibited in both.

525- MF,    Pulsed electromagnetic fields regulate metabolic reprogramming and mitochondrial fission in endothelial cells for angiogenesis
- in-vitro, Nor, HUVECs
*angioG↑, PEMFs promoted a shift in the energy metabolism pattern of HUVECs from oxidative phosphorylation to aerobic glycolysis.
*GPx1↑, 4x
*GPx4↑, 2.2x
*SOD↑, SOD1/2 3.5x
*PFKM↑, 3x
*PFKL↑, 2.5x
*PKM2↑, 2.6x : activation of PKM2 enhanced angiogenesis in endothelial cells (ECs) by modulating glycolysis, mitochondrial fission, and fusion
*PFKP↑, 2.8x
*HK2↑, 4x
*GLUT1↑, 1.5x
*GLUT4↑, 1.6x
*ROS↓, reminder: normal HUVECs cells
*MMP↝, no damage, (normal cells)
*Glycolysis↑, (PFKL, PFKLM, PFKP, PKM2, and HK2) encoding the three key regulatory enzymes of glycolysis, hexokinase, phosphofructokinase, and pyruvate kinase, sharply increased when HUVECs were exposed to PEMFs
*OXPHOS↓, PEMFs promoted a shift in the energy metabolism pattern of HUVECs from oxidative phosphorylation to aerobic glycolysis

5241- MF,    A review on the use of magnetic fields and ultrasound for non-invasive cancer treatment
- Review, Var, NA
other↑, Magnetic fields have been found to stimulate collagen density in and around the joints, and help to trigger Ca2+ flow to the defect site resulting in faster bone healing
BloodF↑, blood microcirculation revealed that magnetic fields have strong influence on relaxation and constriction of capillary blood vessels which alters the blood flow.
Glycolysis↓, In general, the glycolysis and glucose oxidations are decreased in diabetic patients leading to lower ATP production.
ATP↓,
VEGF↓, Application of magnetic fields can significantly decrease VEGF level and therefore reduces the growth and distribution of cancer to other parts of the body
ROS↑, SMF interacts with the charged molecules (ions, proteins etc.) of biological system through several physical mechanisms and alters the activity, concentration, and life time of paramagnetic free radicals i.e. ROS (reactive oxygen species),
P-gp↓, study demonstrated that 8.8 mT SMF enhances cytotoxic potency of Adriamycin on K562 cells due to decrease in the P-gp expression
Apoptosis↑, n vitro analysis in terms of apoptosis and cell electrical properties showed that MCF7 cells are highly reactive to 3 mT flux density and normal cells (MCF10) are unaffected.
selectivity↑,
Ca+2↑, Long PMF (50 Hz, 0.1–1 mT) for 7 days Undifferentiated PC12, increased intracellular Ca+ concentration and Catalase activity.
Catalase↑,

1170- MushCha,    Chaga mushroom extract suppresses oral cancer cell growth via inhibition of energy metabolism
- in-vitro, Oral, HSC4
tumCV↓,
TumCP↓,
TumCCA↑,
STAT3↓,
Glycolysis↓,
MMP↓,
TumAuto↑,
p38↑, Chaga mushroom extract is likely to induce apoptosis via activation of p38 MAPK and NF-κB pathways.
NF-kB↑,

1271- NCL,    Niclosamide inhibits ovarian carcinoma growth by interrupting cellular bioenergetics
- vitro+vivo, Ovarian, SKOV3
Wnt/(β-catenin)↓,
mTOR↓,
STAT3↓,
NF-kB↓,
NOTCH↓,
TumCG↓,
Apoptosis↑,
MEK↓, inactivating MEK1/2-ERK1/2
ERK↓,
mitResp↓,
Glycolysis↓, aerobic glycolysis
ROS↑, abolishment of the excess ROS production with NAC (10 mM) abrogated the Niclosamide-induced cell apoptosis under glucose deprivation
JNK↑,

946- Nimb,    Nimbolide retards T cell lymphoma progression by altering apoptosis, glucose metabolism, pH regulation, and ROS homeostasis
- in-vivo, NA, NA
Apoptosis↑,
Bcl-2↓,
P53↑, up-regulated expression of p53,
cl‑Casp3↑,
Cyt‑c↑,
ROS↑, induced ROS production by suppressing the expression of antioxidant regulatory enzymes, namely superoxide dismutase and catalase
SOD↓,
Catalase↓,
Glycolysis↓,
GLUT3↓,
LDHA↓, LDHA inhibitor
MCT1↓,
NHE1↓,
ATPase↓,
CAIX↓,

968- OA,    Oroxylin A inhibits glycolysis-dependent proliferation of human breast cancer via promoting SIRT3-mediated SOD2 transcription and HIF1α destabilization
- vitro+vivo, BC, MDA-MB-231 - in-vitro, BC, MBT-2
Hif1a↓,
SIRT3↑,
SOD2↑,
GlucoseCon↓, OA inhibit glucose metabolism
Glycolysis↓, SIRT3-associated inhibition of glycolysis
TumCG↓,

991- OA,    Blockade of glycolysis-dependent contraction by oroxylin a via inhibition of lactate dehydrogenase-a in hepatic stellate cells
- in-vivo, NA, NA - in-vivo, Nor, NA
*Glycolysis↓, Oroxylin A blocked aerobic glycolysis in HSCs evidenced by reduction in glucose uptake and consumption and lactate production
*GlucoseCon↓,
*lactateProd↓,
*ECAR↓,
*HK2↓,
*PFK↓, phosphofructokinase 1
*PKM2↓,
*LDHA↓, inhibited the expression and activity of lactate dehydrogenase-A (LDH-A)

2396- PACs,    PKM2 is the target of proanthocyanidin B2 during the inhibition of hepatocellular carcinoma
- in-vitro, HCC, HCCLM3 - in-vitro, HCC, SMMC-7721 cell - in-vitro, HCC, Bel-7402 - in-vitro, HCC, HUH7 - in-vitro, HCC, HepG2 - in-vitro, Nor, L02
TumCP↓, PB2 inhibited the proliferation, induced cell cycle arrest, and triggered apoptosis of HCC cells in vivo and in vitro.
TumCCA↓,
Apoptosis↑,
GlucoseCon↓, PB2 also suppressed glucose uptake and lactate levels via the direct inhibition of the key glycolytic enzyme, PKM2.
lactateProd↓,
PKM2↓,
Glycolysis↓, to suppress aerobic glycolysis
HK2↓, PB2 suppressed the expression of HK2, PFKFB3, and PKM2, while enhancing the expression of OXPHOS in both HCC-LM3 and SMMC-7721 cells
PFK↓,
OXPHOS↑, PB2 inhibited aerobic glycolysis and improved OXPHOS in HCC cell lines
ChemoSen↑, PB2 enhanced the chemosensitivity of SORA on HCC, both in vivo and in vitro
HSP90↓, PB2 reduced the expressions of both HSP90 and HIF-1α in a dose-dependent manner in HCC cells
Hif1a↓,

998- PB,    Phenyl butyrate inhibits pyruvate dehydrogenase kinase 1 and contributes to its anti-cancer effect
- in-vivo, NA, NA
p‑PDH↓,
PDH↑,
PDK1↓,
HDAC↓,
Glycolysis↓, decreased glycolysis in cytoplasm
MMP↓,
Apoptosis↑,

2421- PB,    Sodium butyrate inhibits aerobic glycolysis of hepatocellular carcinoma cells via the c‐myc/hexokinase 2 pathway
- in-vitro, HCC, HCCLM3 - in-vivo, NA, NA - in-vitro, HCC, Bel-7402 - in-vitro, HCC, SMMC-7721 cell - in-vitro, Nor, L02
Glycolysis↓, NaBu inhibited aerobic glycolysis in the HCC cells in vivo and in vitro
Apoptosis↑, NaBu induced apoptosis while inhibiting the proliferation of the HCC cells in vivo and in vitro.
TumCP↓,
lactateProd↓, the compound inhibited the release of lactate and glucose consumption in the HCC cells in vitro and inhibited the production of lactate in vivo.
GlucoseCon↓,
HK2↓, NaBu downregulated HK2 expression via c‐myc signalling.
ChemoSen↑, upregulation of glycolysis in the HCC cells induced by sorafenib was impeded by NaBu, thereby enhancing the anti‐HCC effect of sorafenib in vitro and in vivo.
*toxicity↓, Moreover, NaBu did not affect the mouse serum levels of ALT, AST or creatinine (Figure S2A). Furthermore, no obvious pathological changes were observed in the liver, lung, heart or kidney sections of the NaBu‐treated mice
cMyc↓, mRNA expression of c‐myc was significantly inhibited in both HCC‐LM3 and Bel‐7402 cell lines upon treatment with 3 mM NaBu for 48 h
PFK1↓, Western blotting showed that NaBu treatment for 48 h suppressed the expressions of HK2, PFK1 and LDH-A inthe HCC-LM3 and Bel- 6402 cell lines in a dose- dependent manner
LDHA↓,
cMyc↓, NaBu inhibited the expression of c-myc in the total and nuclear lysate in a dose-depedent manner. NaBu suppressed the expression of c- myc in the tumour tissue
ChemoSen↑, NaBu impairs the enhancement of aerobic glycolysis in the HCC cells by sorafenib and improves the effect of the drug on HCC cells both in vitro and in vivo.

1672- PBG,    The Potential Use of Propolis as an Adjunctive Therapy in Breast Cancers
- Review, BC, NA
ChemoSen↓, 4 human clinical trials that demonstrated the successful use of propolis in alleviating side effects of chemotherapy and radiotherapy while increasing the quality of life of breast cancer patients, with minimal adverse effects.
RadioS↑,
Inflam↓, immunomodulatory, anti-inflammatory, and anti-cancer properties.
AntiCan↑,
Dose∅, Indonesia: IC50 = 4.57 μg/mL and 10.23 μg/mL
mtDam↑, Poland: propolis induced mitochondrial damage and subsequent apoptosis in breast cancer cells.
Apoptosis?,
OCR↓, China: CAPE inhibited mitochondrial oxygen consumption rate (OCR) by reducing basal, maximal, and spare respiration rate and consequently inhibiting ATP production
ATP↓,
ROS↑, Iran: inducing intracellular ROS production, IC50 = 65-96 μg/mL
ROS↑, Propolis induced mitochondrial dysfunction and lactate dehydrogenase release indicating the occurrence of ROS-associated necrosis.
LDH↓,
TP53↓, Interestingly, a reduced expression of apoptosis-related genes such as TP53, CASP3, BAX, and P21)
Casp3↓,
BAX↓,
P21↓,
ROS↑, CAPE: inducing oxidative stress through upregulation of e-NOS and i-NOS levels
eNOS↑,
iNOS↑,
eff↑, The combination of propolis and mangostin significantly reduced the expression of Wnt2, FAK, and HIF-1α, when compared to propolis or mangostin alone
hTERT/TERT↓, downregulation of the mRNA levels of hTERT and cyclin D1
cycD1/CCND1↓,
eff↑, Synergism with bee venom was observed
eff↑, Statistically significant decrease was found in the MCF-7 cell viability 48 h after applying different combinations of cisplatin (3.12 μg/mL) and curcumin (0.31 μg/mL) and propolis (160 μg/mL)
eff↑, Nanoparticles of chrysin had significantly higher cytotoxicity against MCF-7 cells, compared to chrysin
eff↑, Propolis nanoparticles appeared to increase cytotoxicity of propolis against MCF-7 cells
STAT3↓, Chrysin also inhibited the hypoxia-induced STAT3 tyrosine phosphorylation suggesting the mechanism of action was through STAT3 inhibition.
TIMP1↓, Propolis reduced the expression of TIMP-1, IL-4, and IL-10.
IL4↓,
IL10↓,
OS↑, patients supplemented with propolis had significantly longer median disease free survival time (400 mg, 3 times daily for 10 d pre-, during, and post)
Dose∅, 400 mg, 3 times daily for 10 d pre-, during, and post
ER Stress↑, endoplasmic reticulum stress
ROS↑, upregulating the expression of Annexin A7 (ANXA7), reactive oxygen species (ROS) level, and NF-κB p65 level, while simultaneously reducing the mitochondrial membrane potential.
NF-kB↓,
p65↓,
MMP↓,
TumAuto↑, propolis induced autophagy by increasing the expression of LC3-II and reducing the expression of p62 level
LC3II↑,
p62↓,
TLR4↓, propolis downregulates the inflammatory TLR4
mtDam↑, propolis induced mitochondrial dysfunction and lactate dehydrogenase release indicating ROS-associated necrosis in MDA MB-231cancer cells
LDH↓,
ROS↑,
Glycolysis↓, inhibit the proliferation of MDA-MB-231 cells by targeting key enzymes of glycolysis, namely glycolysis-hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase muscle isozyme M2 (PKM2), and lactate dehydrogenase A (LDHA),
HK2↓,
PFK↓,
PKM2↓,
LDH↓,
IL10↓, propolis significantly reduced the relative number of CD4+, CD25+, FoxP3+ regulatory T cells expressing IL-10
HDAC8↓, Chrysin, a propolis bioactive compound, inhibits HDAC8
eff↑, combination of propolis and mangostin significantly reduced the expression of Wnt2, FAK, and HIF-1α, when compared to propolis or mangostin alone.
eff↑, Propolis also upregulated the expression of catalase, HTRA2/Omi, FADD, and TRAIL-associated DR5 and DR4 which significantly enhanced the cytotoxicity of doxorubicin in MCF-7 cells
P21↑, Chrysin, a propolis bioactive compound, inhibits HDAC8 and significantly increases the expression of p21 (waf1/cip1) in breast cancer cells, leading to apoptosis.

1661- PBG,    Propolis: a natural compound with potential as an adjuvant in cancer therapy - a review of signaling pathways
- Review, Var, NA
JNK↓, downregulating pathways involving Jun-N terminal kinase, ERK1/2, Akt and NF-ƘB
ERK↓,
Akt↓,
NF-kB↓,
FAK↓, inhibiting Wtn2 and FAK, and MAPK and PI3K/AKT signaling pathways
MAPK↓,
PI3K↓,
Akt↓,
P21↑, propolis-induced up-regulation of p21 and p27
p27↑,
TRAIL↑, effects of propolis are mediated through upregulation of TRAIL, Bax, p53, and downregulation of the ERK1/2 signaling
BAX↑,
P53↑,
ERK↓,
ChemoSen↑, effective adjuvant therapy aimed at reducing related side effects associated with chemotherapy and radiotherapy
RadioS↑,
Glycolysis↓, Chinese poplar propolis decreased aerobic glycolysis by reducing the levels of crucial enzymes such as phosphofructokinase (PFK), hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA)
HK2↓,
PKM2↓,
LDHA↓,
PFK↓,

2382- PBG,    Integration with Transcriptomic and Metabolomic Analyses Reveals the In Vitro Cytotoxic Mechanisms of Chinese Poplar Propolis by Triggering the Glucose Metabolism in Human Hepatocellular Carcinoma Cells
- in-vitro, HCC, HepG2
TumCP↓, Our evidence suggested that CP possesses a great potential to inhibit the proliferation of HepG2 cells by targeting the glucose metabolism.
Glycolysis↓,
GlucoseCon↓, CP effectively restrained glucose consumption and lactic acid production.
lactateProd↓,
GLUT1↓, CP treatment led to a substantial decrease in the mRNA expression levels of key glucose transporters (GLUT1 and GLUT3) and glycolytic enzymes (LDHA, HK2, PKM2, and PFK).
GLUT2↓,
LDHA↓,
HK2↓,
PKM2↓,
PFK↓,
Dose↝, key compounds in CP were screened, and apigenin, pinobanksin, pinocembrin, and galangin were identified as potential active agents against glycolysis.

2381- PBG,    Chinese Poplar Propolis Inhibits MDA-MB-231 Cell Proliferation in an Inflammatory Microenvironment by Targeting Enzymes of the Glycolytic Pathway
- in-vitro, BC, MDA-MB-231
TumCP↓, Propolis treatment obviously inhibited MDA-MB-231 cell proliferation, migration and invasion, clone forming, and angiogenesis.
TumCMig↓,
TumCI↓,
angioG↓,
TNF-α↓, (TNF-α), interleukin (IL)-1β, and IL-6, as well as NLRP3 inflammasomes, were decreased following propolis treatment when compared with the LPS group.
IL1β↓,
IL6↓,
NLRP3↓,
Glycolysis↓, Moreover, propolis treatment significantly downregulated the levels of key enzymes of glycolysis–hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase muscle isozyme M2 (PKM2), and lactate dehydrogenase A (LDHA) in MDA-MB-231 cells
HK2↓,
PFK↓,
PKM2↓,
LDHA↓,
ROS↑, propolis increased reactive oxygen species (ROS) levels and decreased mitochondrial membrane potential.
MMP↓,

2380- PBG,    Potential Strategies for Overcoming Drug Resistance Pathways Using Propolis and Its Polyphenolic/Flavonoid Compounds in Combination with Chemotherapy and Radiotherapy
- Review, Var, NA
Hif1a↓, Flavonoid components from propolis, as inhibitors of HIF-1, have the ability to regulate critical glycolytic components in cancer cells, including (PKM2), (LDHA), (GLUTs), (HKII), (PFK-1), and (PDK)
Glycolysis↓,
PKM2↓,
LDHA↓,
GLUT2↓,
HK2↓,
PFK1↓,
PDK1↓,
chemoP↓, The positive effects of combining propolis with chemotherapeutics include reduced cytotoxicity to peripheral blood leukocytes, liver, and kidney cells.
radioP↑, Their selective nature makes them suitable for protecting normal cells while inducing cell death in cancer cells during chemotherapy or radiotherapy.

3252- PBG,    Propolis Extract and Its Bioactive Compounds—From Traditional to Modern Extraction Technologies
- Review, NA, NA
*Inflam↓, extracts act by suppressing similar targets, from pro-inflammatory TNF/NF-κB to the pro-proliferative MAPK/ERK pathway.
*TNF-α↓,
*NF-kB↓,
*MAPK↓,
*ERK↓,
*antiOx↑, they activate similar antioxidant mechanisms of action, like Nrf2-ARE intracellular antioxidant pathway,
*NRF2↑,
*cardioP↑, pinocembrin was shown to be cardioprotective by enhancing glycolysis in the myocardium, which is an essential mechanism of action against ischemic injury of the heart
*Glycolysis↑,
*Ca+2↓, Reducing the content of Ca2+ in mitochondria prevents mitochondrial membrane swelling,
*HO-1↑, CAPE is beneficial as an antioxidant and the inductor of heme oxygenase-1 (HO), Nrf2-regulated gene
*NRF2↑,
*neuroP↑, HO-1 induction results in cardioprotective effects in diabetes [80], neuroprotective in microglial cells

4922- PEITC,    Phenethyl Isothiocyanate: A comprehensive review of anti-cancer mechanisms
- Review, Var, NA
Risk↓, strong inverse relationship between dietary intake of cruciferous vegetables and the incidence of cancer.
AntiCan↑, Phenethyl isothiocyanate (PEITC) is present as gluconasturtiin in many cruciferous vegetables with remarkable anti-cancer effects.
TumCP↓, PEITC targets multiple proteins to suppress various cancer-promoting mechanisms such as cell proliferation, progression and metastasis
TumMeta↓,
ChemoSen↑, combination of PEITC with conventional anti-cancer agents is also highly effective in improving overall efficacy
*BioAv↑, ITCs are released from glucosinolates by the action of the enzyme myrosinase. The enzyme myrosinase can be activated by cutting or chewing the vegetables, but heating can destroy its activity
*other↝, Although water cress and broccoli are known to be the richest source, PEITC can also be obtained from turnips and radish
*Dose↝, In a study conducted with human volunteers, approximately 2 to 6 mg of PEITC was found to be released by the consumption of one ounce of watercress
Dose↓, significant anti-cancer effects can be achieved at micromolar concentrations of PEITC.
*BioAv↑, PEITC is highly bioavailable after oral administration. A single dose of 10–100 μmol/kg PEITC in rats resulted in bioavailability ranging between 90–114%
*Dose↝, Furthermore, about 928.5±250nM peak plasma concentration of PEITC was achieved in human subjects, after the consumption of 100g watercress.
*Half-Life↝, time to reach peak plasma concentration was observed to be 2.6h±1.1h with a t1/2 4.9±1.1h
*toxicity↝, long term studies are required to establish the safety profile of PEITC, since regular intake of PEITC can cause its accumulation resulting in cumulative effects, which could be toxic.
GSH↓, The conjugation of PEITC with intracellular glutathione and the subsequent removal of the conjugate result in depletion of glutathione and alteration in redox homeostasis leading to oxidative stress
ROS↑, PEITC-mediated generation of reactive oxygen species (ROS) is known to be a general mechanism of action leading to cytotoxic effects, especially specific to cancer cells
CYP1A1↑, PEITC on one hand causes induction of CYP1A1 and CYP1A2; however, it inhibits activity of certain CytP450 enzymes, such as CYP2E1, CYP3A4 and CYP2A3
CYP1A2↑,
P450↓,
CYP2E1↑,
CYP3A4↓,
CYP2A3/CYP2A6↓,
*ROS↓, PEITC treatment caused a significant increase in the activities of ROS detoxifying enzymes such as glutathione peroxidase1, superoxide dismutase 1 and 2. This was also confirmed in human study where subjects were administered watercress, a major sour
*GPx1↑,
*SOD1↑,
*SOD2↑,
Akt↓, PEITC inhibits Akt, a component of Ras signaling to inhibit tumor growth in several cancer types
EGFR↓, PEITC is also known to inhibit EGFR and HER2, which are important growth factors and regulators of Akt in different cancer models
HER2/EBBR2↓,
P53↑, PEITC-mediated activation of another tumor suppressor, p53 was observed in oral squamous cell carcinoma, causing G0/G1 phase arrest in multiple myeloma,
Telomerase↓, PEITC has been shown to inhibit telomerase activity in prostate and cervical cancer cells
selectivity↑, generation of reactive oxygen species (ROS), which also has been shown to be the basis of selectivity of PEITC toward cancer cells leaving normal cells undamaged [
MMP↓, ROS generation by PEITC leads to mitochondrial deregulation and modulation of proteins like Bcl2, BID, BIM and BAX, causing the release of cytochrome c into cytosol leading to apoptosis
Cyt‑c↑,
Apoptosis↑,
DR4↑, induction of death receptors and Fas-mediated apoptosis
Fas↑,
XIAP↓, PEITC-mediated suppression of anti-apoptotic proteins like XIAP and survivin, which are up-regulated in cancer cells
survivin↓,
TumAuto↑, PEITC induces autophagic cell death in cancer cells
Hif1a↓, PEITC directly or indirectly suppresses HIF1α
angioG↓, is possible that PEITC can block angiogenesis by non-hypoxic mechanisms also.
MMPs↓, Various studies with PEITC have shown suppression of invasion through inhibition of matrix metalloproteinases along with anti-metastatic effects caused by suppression of ERK kinase activity and transcriptional activity of NFkB
ERK↓,
NF-kB↓,
EMT↓, PEITC was also known to inhibit processes, such as epithelial to mesenchymal transition (EMT), cell invasion and migration, which are essential pre-requisites for metastasis
TumCI↓,
TumCMig↓,
Glycolysis↓, reduced rates of glycolysis in PEITC-treated cells and depletion of ATP lead to death in prostate cancer cells
ATP↓,
selectivity↑, PEITC (5μM) treatment suppressed glycolysis in the cancer cells, but no changes were observed in normal cells.
*antiOx↑, the antioxidant effect is achieved at very low ITC levels in normal cells as shown in various animal models
Dose↝, At higher concentrations, ITCs may generate ROS by depleting antioxidant levels. PEITC is known to cause ROS generation, which is the major mechanism of toxicity in cancer cells
other↝, There is a continuous leakage of electrons from the electron transport chain (ETC), which is major source of ROS production. PEITC causes generation of endogenous ROS by disrupting mitochondrial respiratory chain
OCR↓, PEITC also inhibits mitochondrial complex III activity and reduces the oxygen consumption rate in prostate cancer cells
GSH↓, PEITC binds to GSH and causes its depletion in cancer cells leading to ROS-induced cell damage
ITGB1↓, PEITC was found to inhibit major integrins, such as ITGB1, ITGA2 and ITGA6 in prostate cancer cells
ITGB6↓,
ChemoSen↑, Using pre-clinical studies, improved outcomes were observed when the conventional agents, such as docetaxel, metformin, vinblastine, doxorubicin and HDAC inhibitors were combined with PEITC

2946- PL,    Piperlongumine, a potent anticancer phytotherapeutic: Perspectives on contemporary status and future possibilities as an anticancer agent
- Review, Var, NA
ROS↑, piperlongumine inhibits cancer growth by resulting in the accumulation of intracellular reactive oxygen species, decreasing glutathione and chromosomal damage, or modulating key regulatory proteins, including PI3K, AKT, mTOR, NF-kβ, STATs, and cycD
GSH↓, reduced glutathione (GSH) levels in mouse colon cancer cells
DNAdam↑,
ChemoSen↑, combined treatment with piperlongumine potentiates the anticancer activity of conventional chemotherapeutics and overcomes resistance to chemo- and radio- therapy
RadioS↑, piperlongumine treatment enhances ROS production via decreasing GSH levels and causing thioredoxin reductase inhibition
BioEnh↑, Moreover, the bioavailability is significantly improved after oral administration of piperlongumine
selectivity↑, It shows selectivity toward human cancer cells over normal cells and has minimal side effects
BioAv↓, ts low aqueous solubility affects its anti-cancer activity by limiting its bioavailability during oral administration
eff↑, encapsulation of piperlongumine in another biocompatible natural polymer, chitosan, has been found to result in pH-dependent piperlongumine release and to enhance cytotoxicity via efficient intracellular ROS accumulation against human gastric carcin
p‑Akt↓, Fig 2
mTOR↓,
GSK‐3β↓,
β-catenin/ZEB1↓,
HK2↓, iperlongumine treatment decreases cell proliferation, single-cell colony-formation ability, and HK2-mediated glycolysis in NSCLC cells via inhibiting the interaction between HK2 and voltage-dependent anion channel 1 (VDAC1)
Glycolysis↓,
Cyt‑c↑,
Casp9↑,
Casp3↑,
Casp7↑,
cl‑PARP↑,
TrxR↓, piperlongumine (4 or 12 mg/kg/day for 15 days) administration significantly inhibits increase in tumor weight and volume with less TrxR1 activity in SGC-7901 cell
ER Stress↑,
ATF4↝,
CHOP↑, activating the downstream ER-MAPK-C/EBP homologous protein (CHOP) signaling pathway
Prx4↑, piperlongumine kills high-grade glioma cells via oxidative inactivation of PRDX4 mediated ROS induction, thereby inducing intracellular ER stress
NF-kB↓, piperlongumine treatment (2.5–5 mg/ kg body weight) decreases the growth of lung tumors via inhibition of NF-κB
cycD1/CCND1↓, decreases expression of cyclin D1, cyclin- dependent kinase (CDK)-4, CDK-6, p- retinoblastoma (p-Rb)
CDK4↓,
CDK6↓,
p‑RB1↓,
RAS↓, piperlongumine downregulates the expression of Ras protein
cMyc↓, inhibiting the activity of other related proteins, such as Akt/NF-κB, c-Myc, and cyclin D1 in DMH + DSS induced colon tumor cells
TumCCA↑, by arresting colon tumor cells in the G2/M phase of the cell cycle
selectivity↑, hows more selective cytotoxicity against human breast cancer MCF-7 cells than human breast epithelial MCF-10A cells
STAT3↓, thus inducing inhibition of the STAT3 signaling pathway in multiple myeloma cells
NRF2↑, Nrf2) activation has been found to mediate the upregulation of heme oxygenase-1 (HO-1) in piperlongumine treated MCF-7 and MCF-10A cells
HO-1↑,
PTEN↑, stimulates ROS accumulation; p53, p27, and PTEN overexpression
P-gp↓, P-gp, MDR1, MRP1, survivin, p-Akt, NF-κB, and Twist downregulation;
MDR1↓,
MRP1↓,
survivin↓,
Twist↓,
AP-1↓, iperlongumine significantly suppresses the expression of transcription factors, such as AP-1, MYC, NF-κB, SP1, STAT1, STAT3, STAT6, and YY1.
Sp1/3/4↓,
STAT1↓,
STAT6↓,
SOX4↑, increased expression of p21, SOX4, and XBP in B-ALL cells
XBP-1↑,
P21↑,
eff↑, combined use of piperlongumine with cisplatin enhances the sensitivity toward cisplatin by inhibiting Akt phosphorylation
Inflam↓, inflammation (COX-2, IL6); invasion and metastasis, such as ICAM-1, MMP-9, CXCR-4, VEGF;
COX2↓,
IL6↓,
MMP9↓,
TumMeta↓,
TumCI↓,
ICAM-1↓,
CXCR4↓,
VEGF↓,
angioG↓,
Half-Life↝, The analysis of the plasma of piperlongumine treated mice (50 mg/kg) after intraperitoneal administration, 1511.9 ng/ml, 418.2 ng/ml, and 41.9 ng/ml concentrations ofplasma piperlongumine were found at 30 minutes, 3 hours, and 24 hours, respecti
BioAv↑, Moreover, the bioavailability is significantly improved after oral administration of piperlongumine

2948- PL,    The promising potential of piperlongumine as an emerging therapeutics for cancer
- Review, Var, NA
tumCV↓, inhibit different hallmarks of cancer such as cell survival, proliferation, invasion, angiogenesis, epithelial-mesenchymal-transition, metastases,
TumCP↓,
TumCI↓,
angioG↓,
EMT↓,
TumMeta↓,
*hepatoP↑, A study demonstrated the hepatoprotective effects of P. longum via decreasing the rate of lipid peroxidation and increasing glutathione (GSH) levels
*lipid-P↓,
*GSH↑,
cardioP↑, cardioprotective effect
CycB/CCNB1↓, downregulated the mRNA expression of the cell cycle regulatory genes such as cyclin B1, cyclin D1, cyclin-dependent kinases (CDK)-1, CDK4, CDK6, and proliferating cell nuclear antigen (PCNA)
cycD1/CCND1↓,
CDK2↓,
CDK1↓,
CDK4↓,
CDK6↓,
PCNA↓,
Akt↓, suppression of the Akt/mTOR pathway by PL was also associated with the partial inhibition of glycolysis
mTOR↓,
Glycolysis↓,
NF-kB↓, Suppression of the NF-κB signaling pathway and its related genes by PL was reported in different cancers
IKKα↓, inactivation of the inhibitor of NF-κB kinase subunit beta (IKKβ)
JAK1↓, PL efficiently inhibited cell proliferation, invasion, and migration by blocking the JAK1,2/STAT3 signaling pathway
JAK2↓,
STAT3↓,
ERK↓, PL also negatively regulates ERK1/2 signaling pathways, thereby suppressing the level of c-Fos in CRC cells
cFos↓,
Slug↓, PL was found to downregulate slug and upregulate E-cadherin and inhibited epithelial-mesenchymal transition (EMT) in breast cancer cells
E-cadherin↑,
TOP2↓, ↓topoisomerase II, ↑p53, ↑p21, ↓Bcl-2, ↑Bax, ↑Cyt C, ↑caspase-3, ↑caspase-7, ↑caspase-8
P53↑,
P21↑,
Bcl-2↓,
BAX↑,
Casp3↑,
Casp7↑,
Casp8↑,
p‑HER2/EBBR2↓, ↓p-HER1, ↓p-HER2, ↓p-HER3
HO-1↑, ↑Apoptosis, ↑HO-1, ↑Nrf2
NRF2↑,
BIM↑, ↑BIM, ↑cleaved caspase-9 and caspase-3, ↓p-FOXO3A, ↓p-Akt
p‑FOXO3↓,
Sp1/3/4↓, ↑apoptosis, ↑ROS, ↓Sp1, ↓Sp3, ↓Sp4, ↓cMyc, ↓EGFR, ↓survivin, ↓cMET
cMyc↓,
EGFR↓,
survivin↓,
cMET↓,
NQO1↑, G2/M phase arrest, ↑apoptosis, ↑ROS, ↓p-Akt, ↑Bad, ↓Bcl-2, ↑NQO1, ↑HO-1, ↑SOD2, ↑p21, ↑p-ERK, ↑p-JNK,
SOD2↑,
TrxR↓, G2/M cell cycle arrest, ↑apoptosis, ↑ROS, ↓GSH, ↓TrxR
MDM2↓, ↑ROS, ↓MDM-2, ↓cyclin B1, ↓Cdc2, G2/M phase arrest, ↑p-eIF2α, ↑ATF4, KATO III ↑CHOP, ↑apoptosis
p‑eIF2α↑,
ATF4↑,
CHOP↑,
MDA↑, ↑ROS, ↓TrxR1, ↑cleaved caspase-3, ↑CHOP, ↑MDA
Ki-67↓, ↓Ki-67, ↓MMP-9, ↓Twist,
MMP9↓,
Twist↓,
SOX2↓, ↓SOX2, ↓NANOG, ↓Oct-4, ↑E-cadherin, ↑CK18, ↓N-cadherin, ↓vimentin, ↓snail, ↓slug
Nanog↓,
OCT4↓,
N-cadherin↓,
Vim↓,
Snail↓,
TumW↓, ↓Tumor weight, ↓tumor growth
TumCG↓,
HK2↓, ↓HK2
RB1↓, ↓Rb
IL6↓, ↓IL-6, ↓IL-8,
IL8↓,
SOD1↑, ↑SOD1
RadioS↑, ombination with PL, very low intensity of radiation is found to be effective in cancer cells
ChemoSen↑, PL as a chemosensitizer which sensitized the cancer cells towards the commercially available chemotherapeutics
toxicity↓, PL does not have any adverse effect on the normal functioning of the liver and kidney.
Sp1/3/4↓, In vitro SKBR3 ↓Sp1, ↓Sp3, ↓Sp4
GSH↓, In vitro MCF-7 ↓CDK1, G2/M phase arrest ↓CDK4, ↓CDK6, ↓PCNA, ↓p-CDK1, ↑cyclin B1, ↑ROS, ↓GSH, ↓p-IκBα,
SOD↑, In vitro PANC-1, MIA PaCa-2 ↑ROS, ↑SOD1, ↑GSTP1, ↑HO-1

992- PL,    Piperlongumine based nanomedicine impairs glycolytic metabolism in triple negative breast cancer stem cells through modulation of GAPDH & FBP1
- in-vivo, BC, NA
EPR↓,
Glycolysis↓,
GAPDH↓,
GSTP1/GSTπ↝,
FBPase↑, upregulation of fructose-1,6-bisphosphatase 1 (FBP1), a rate-limiting enzyme in gluconeogenesis.

2409- PTS,    Pterostilbene Induces Pyroptosis in Breast Cancer Cells through Pyruvate Kinase 2/Caspase-8/Gasdermin C Signaling Pathway
- in-vitro, BC, EMT6 - in-vitro, BC, 4T1 - in-vitro, Nor, HC11
Pyro↑, PTE induced pyroptosis by inhibiting tumor glycolysis
Glycolysis↓, demonstrated that PTE inhibited the glycolysis of tumor tissue.
*toxicity∅, we tested the toxicity of PTE to HC11. The result showed that PTE did not affect the viability of HC11 (p > 0.05, Figure 2G) and indicated that PTE was non-toxic to mouse mammary epithelial cells.
selectivity↑,
GSDMC↑, The above experiments had demonstrated that PTE activated GSDMC
PKM2↓, Our results showed that PTE down-regulated the expression of PKM2 and upregulate the expression of PKM1 in tumor cells
PKM1↑,
GlucoseCon↓, PTE induced pyroptosis in mouse breast xenografts. Colorimetric kit results showed that PTE down-regulated glucose consumption, lactate production, and ATP content
lactateProd↓,
ATP↓,
TumCG↓, PTE inhibits the growth of mouse breast xenografts in vivo.

3374- QC,    Therapeutic effects of quercetin in oral cancer therapy: a systematic review of preclinical evidence focused on oxidative damage, apoptosis and anti-metastasis
- Review, Oral, NA - Review, AD, NA
α-SMA↓, In oral cancer cells, quercetin could inhibit EMT via up-regulation of claudin-1 and E-cadherin and down-regulation of α-SMA, vimentin, fibronectin, and Slug [29]
α-SMA↑, OSC20 Invasion: ↓Migration, ↑Expression of epithelial markers (E-cadherin & claudin-1), ↑Expression of mesenchymal markers (fibronectin, vimentin, & α-SMA),
TumCP↓, quercetin significantly reduced cancer cell proliferation, cell viability, tumor volume, invasion, metastasis and migration
tumCV↓,
TumVol↓,
TumCI↓,
TumMeta↓,
TumCMig↓,
ROS↑, This anti-cancer agent induced oxidative stress and apoptosis in the cancer cells.
Apoptosis↑,
BioAv↓, The efficacy of quercetin (as lipophilic) is much impacted by its poor absorption rates, which define its bioavailability. The research on quercetin's bioavailability in animal models shows it may be as low as 10%
*neuroP↑, quercetin has been observed to exhibit neuroprotective effects in Alzheimer's disease through its anti-oxidants, and anti-inflammatory properties and inhibition of amyloid-β (Aβ) fibril formation
*antiOx↑,
*Inflam↓,
*Aβ↓,
*cardioP↑, Additionally, quercetin protects the heart by stopping oxidative stress, inflammation, apoptosis, and protein kinases
MMP↓, ↓MMP, ↑Cytosolic Cyt. C,
Cyt‑c↑,
MMP2↓, ↓Activation MMP-2 & MMP-9, ↓Expression levels of EMT inducers & MMPs, Downregulated Twist & Slug
MMP9↓,
EMT↓,
MMPs↓,
Twist↓,
Slug↓,
Ca+2↑, ↑Apoptosis, ↑ROS, ↑Ca2+ production, ↑Activities of caspase‑3, caspase‑8 & caspase‑9
AIF↑, ↑Mitochondrial release of Cyt. C, AIF, & Endo G
Endon↑,
P-gp↓, ↓ Protein levels of P-gp, & P-gp Expression
LDH↑, ↑LDH release
HK2↓, CAL27 cells) 80µM/24h Molecular markers: ↓Activities of HK, PK, & LDH, ↓Glycolysis, ↓Glucose uptake, ↓Lactate production, ↓Viability, ↓G3BP1, & YWHA2 protein levels
PKA↓,
Glycolysis↓,
GlucoseCon↓,
lactateProd↓,
GRP78/BiP↑, Quercetin controls the activation of intracellular Ca2+ and calpain-1, which then activates GRP78, caspase-12, and C/EBP homologous protein (CHOP) in oral cancer cells
Casp12↑,
CHOP↑,

910- QC,    The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism
tumCV↓,
Apoptosis↑,
PI3k/Akt/mTOR↓, QUE induces cell death by inhibiting PI3K/Akt/mTOR and STAT3 pathways in PEL cells
Wnt/(β-catenin)↓, reducing β-catenin
MAPK↝,
ERK↝, ERK1/2
TumCCA↑, cell cycle arrest at the G1 phase
H2O2↑,
ROS↑,
TumAuto↑,
MMPs↓, Consistently, QUE was able to reduce the protein levels of MMP-2, MMP-9, VEGF and mTOR, and p-Akt in breast cancer cell lines
P53↑,
Casp3↑,
Hif1a↓, by inactivating the Akt-mTOR pathway [64,74] and HIF-1α
cFLIP↓,
IL6↓, QUE decreased the release of interleukin-6 (IL-6) and IL-10
IL10↓,
lactateProd↓,
Glycolysis↓, It is suggested that QUE alters glucose metabolism by inhibiting monocarboxylate transporter (MCT) activity
PKM2↓,
GLUT1↓,
COX2↓,
VEGF↓,
OCR↓,
ECAR↓,
STAT3↓,
MMP2↓, Consistently, QUE was able to reduce the protein levels of MMP-2, MMP-9, VEGF and mTOR, and p-Akt in breast cancer cell lines
MMP9:TIMP1↓,
mTOR↓,

1201- QC,    Quercetin: a silent retarder of fatty acid oxidation in breast cancer metastasis through steering of mitochondrial CPT1
- in-vivo, BC, NA
mitResp↓, significant reduction in the intracellular mitochondrial respiration
Glycolysis↓,
ATP↓,
ROS↑,
GSH↓,
TumMeta↓,
Apoptosis↑,
FAO↓,

2300- QC,    Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
- Review, Var, NA
AntiTum↑, Quercetin exerts promising anti-tumor effects via the regulation of various cancer signaling pathways
Hif1a↓, Quercetin inhibited HIF-1 transcriptional activity in the HCT116 colon cancer cell line
*Hif1a↑, On the contrary, quercetin increased the accumulation of HIF-1α in healthy cells
Glycolysis↓, Quercetin inhibited glycolysis and proliferation of glycolysis-dependent hepatocellular carcinoma (SMMC-7721 and Bel-7402) cells by downregulating HKII;
HK2↓,
PDK3↓, quercetin inhibited PDK3 in hepatocellular carcinoma (HepG2) and lung cancer (A549) cells
PFKP?, The ability of quercetin to impair PFKP-LDHA signaling

2340- QC,    Oral Squamous Cell Carcinoma Cells with Acquired Resistance to Erlotinib Are Sensitive to Anti-Cancer Effect of Quercetin via Pyruvate Kinase M2 (PKM2)
- in-vitro, OS, NA
TumCG↓, At a concentration of 5 μM, quercetin effectively arrested cell growth, reduced glucose utilization, and inhibited cellular invasiveness
GlucoseCon↓,
TumCI↓,
GLUT1↓, Quercetin also prominently down-regulated GLUT1, PKM2, and lactate dehydrogenase A (LDHA) expression of erlotinib-resistant HSC-3 cells
PKM2↓,
LDHA↓,
Glycolysis↓, Moreover, quercetin (30 μM) suppressed glycolysis in the MCF-7 and MDA-MB-231 breast cancer cells, as evidenced by decreased glucose uptake and lactate production with a concomitant decrease in the levels of the GLUT1, PKM2, and LDHA proteins [29].
lactateProd↓,
HK2↓, Hexokinase 2 (HK2)-mediated glycolysis was also shown to be inhibited following quercetin treatment (25~50 μM) in Bel-7402 and SMMC-7721 hepatocellular carcinoma (HCC) cells
eff↑, Downregulation of PKM2 also potently restored sensitivity to the inhibitory effect of erlotinib on cell growth and invasion

2341- QC,    Quercetin suppresses the mobility of breast cancer by suppressing glycolysis through Akt-mTOR pathway mediated autophagy induction
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
MMP2↓, quercetin treatment down-regulated the expression of cell migration marker proteins, such as matrix metalloproteinase 2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF).
MMP9↓, level of MMP-2, MMP-9 and VEGF was all strongly cut down by quercetin treatment compared with control group
VEGF↓,
Glycolysis↓, quercetin successfully blocked cell glycolysis by inhibiting the level of glucose uptake and the production of lactic acid
lactateProd↓,
PKM2↓, and also decreased the level of glycolysis-related proteins Pyruvate kinase M2 (PKM2), Glucose transporter1(GLUT1) and Lactate dehydrogenase A (LDHA).
GLUT1↓,
LDHA↓,
TumAuto↑, quercetin induced obvious autophagy via inactivating the Akt-mTOR pathway
Akt↓,
mTOR↓,
TumMeta↓, Quercetin suppressed the progression of breast cancer by inhibiting tumor metastasis and glycolysis in vivo
MMP3↓, quercetin effectively suppressed the invasion and migration ability of breast cancer cells through suppressing the expression of MMP-3, MMP-9 and VEGF,
eff↓, down-regulating the expression of PKM2, which regulated the final step of glycolysis, could effectively enhance the chemotherapeutic effect of THP
GlucoseCon↓, we found that quercetin effectively suppressed the level of glucose uptake and the production of lactic acid, and also down-regulated the expression of glycolysis-related proteins PKM2, LDHA and GLUT1,
lactateProd↓,
TumAuto↑, quercetin treatment induced obvious autophagy in MCF-7 and MDA-MB-231 cells via inactivating the Akt-mTOR pathway
LC3B-II↑, showing obvious conversion of LC3B-I to LC3B-II

2342- QC,    Quercetin Inhibits the Proliferation of Glycolysis-Addicted HCC Cells by Reducing Hexokinase 2 and Akt-mTOR Pathway
- in-vitro, HCC, Bel-7402 - in-vitro, HCC, SMMC-7721 cell - in-vivo, NA, NA
TumCP↓, In the present study, we reported that QUE inhibited the proliferation of HCC cells that relied on aerobic glycolysis.
HK2↓, QUE could decrease the protein levels of HK2 and suppress the AKT/mTOR pathway in HCC cells
Akt↓,
mTOR↓,
GlucoseCon↓, glucose uptake and lactate production of SMMC-7721 and Bel-7402 decreased in a dose-dependent manner after QUE treatment
lactateProd↓,
Glycolysis↓, QUE can inhibit the glycolysis of cancer cells, thereby inhibiting the progression of multiple cancers

2344- QC,    Quercetin: A natural solution with the potential to combat liver fibrosis
- Review, Nor, NA
*HK2↓, By reducing the activity of key glycolytic enzymes—including hexokinase II (HK2), phosphofructokinase platelet (PFKP), and pyruvate kinase M2 (PKM2)—quercetin lowers energy production in LSECs, potentially slowing fibrosis progression.
*PFKP↓,
*PKM2↓,
*hepatoP↑, Quercetin lowered levels of liver enzymes (ALT, AST) and total bile acid, markers of liver injury.
*ALAT↓,
*AST↓,
*Glycolysis↓, quercetin inhibited glycolysis in LSECs, reducing lactate production, glucose consumption, and the expression of glycolytic enzymes
*lactateProd↓,
*GlucoseCon↓,
*CXCL1↓, By suppressing CXCL1 secretion, quercetin decreased neutrophil infiltration, a key factor in liver fibrosis, thereby effecting inflammation control.
*Inflam↓,

993- RES,    Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells
- in-vitro, CRC, Caco-2 - in-vivo, Nor, HCEC 1CT
TumCG↓,
Glycolysis↓,
PPP↓,
ATP↑, significant increase (20%) in ATP production
PDH↑, Resveratrol targets the pyruvate dehydrogenase (PDH) complex, a key mitochondrial gatekeeper of energy metabolism, leading to an enhanced PDH activity.
Ca+2↝, resveratrol is a potent modulator of many cellular Ca2+ signaling pathways. Ca2+ is a key mediator of the effect of resveratrol on the oxidative capacity of colon cancer cells.
TumCP↓,
lactateProd↓,
OCR↑, increase of oxygen consumption rate (OCR) both in normal colonic epithelial HCEC 1CT cells
ECAR↓, Following treatment with resveratrol (10 µM, 48 hr), the ECAR was unchanged in normal HCEC 1CT cells, whereas it was significantly reduced (31%) in HCEC 1CT RPA cells ****
*ECAR∅, Following treatment with resveratrol (10 µM, 48 hr), the ECAR was unchanged in normal HCEC 1CT cells
*other?, Resveratrol promotes a shift from respiration to glycolysis in cancer-like cells, but not in normal colonocytes
cycE/CCNE↑, Resveratrol inhibited cell cycle progression by enhancing the levels of cyclin E and cyclin A
cycA1/CCNA1↑,
TumCCA↑,
cycD1/CCND1↑, and by decreasing cyclin D1
OXPHOS↑, Taken together, these observations indicate that exposure to resveratrol leads to a metabolic reorientation from aerobic glycolysis toward OXPHOS.

2333- RES,    Resveratrol regulates insulin resistance to improve the glycolytic pathway by activating SIRT2 in PCOS granulosa cells
- in-vitro, Nor, NA
*glucose↓, RES played a protective role on the IR in PCOS rats, which significantly decreased the levels of blood glucose and serum insulin, up regulated the expression of IGF1R, and down regulated the expression of IGF1.
*Insulin↓,
*IGFR↓,
*IGF-1↓,
*LDHA↑, RES overtly repaired the glycolysis process by reversing the levels of lactic acid and pyruvate, together with up regulating the expression level of LDHA, HK2, and PKM2, after AGK2 treatment.
*HK2↑,
*PKM2↑,
*Glycolysis↝, RES could eectively improve insulin resistance and restore the glycolysis pathway by regulating SIRT2, which may contribute to attenuating the ovarian damage of PCOS rat
*SIRT2↑, activating SIRT2 in PCOS granulosa cells

2332- RES,    Resveratrol’s Anti-Cancer Effects through the Modulation of Tumor Glucose Metabolism
- Review, Var, NA
Glycolysis↓, Resveratrol reduces glucose uptake and glycolysis by affecting Glut1, PFK1, HIF-1α, ROS, PDH, and the CamKKB/AMPK pathway.
GLUT1↓, resveratrol reduces glycolytic flux and Glut1 expression by targeting ROS-mediated HIF-1α activation in Lewis lung carcinoma tumor-bearing mice
PFK1↓,
Hif1a↓, Resveratrol specifically suppresses the nuclear β-catenin protein by inhibiting HIF-1α
ROS↑, Resveratrol increases ROS production
PDH↑, leading to increased PDH activity, inhibiting HK and PFK, and downregulating PKM2 activity
AMPK↑, esveratrol elevated NAD+/NADH, subsequently activated Sirt1, and in turn activated the AMP-activated kinase (AMPK),
TumCG↓, inhibits cell growth, invasion, and proliferation by targeting NF-kB, Sirt1, Sirt3, LDH, PI-3K, mTOR, PKM2, R5P, G6PD, TKT, talin, and PGAM.
TumCI↓,
TumCP↓,
p‑NF-kB↓, suppressing NF-κB phosphorylation
SIRT1↑, Resveratrol activates the target subcellular histone deacetylase Sirt1 in various human tissues, including tumors
SIRT3↑,
LDH↓, decreases glycolytic enzymes (pyruvate kinase and LDH) in Caco2 and HCT-116 cells
PI3K↓, Resveratrol also targets “classical” tumor-promoting pathways, such as PI3K/Akt, STAT3/5, and MAPK, which support glycolysis
mTOR↓, AMPK activation further inhibits the mTOR pathway
PKM2↓, inhibiting HK and PFK, and downregulating PKM2 activity
R5P↝,
G6PD↓, G6PDH knockdown significantly reduced cell proliferation
TKT↝,
talin↓, induces apoptosis by targeting the pentose phosphate and talin-FAK signaling pathways
HK2↓, Resveratrol downregulates glucose metabolism, mainly by inhibiting HK2;
GRP78/BiP↑, resveratrol stimulates GRP-78, and decreases glucose uptake,
GlucoseCon↓,
ER Stress↑, resveratrol-induced ER-stress leads to apoptosis of CRC cells
Warburg↓, Resveratrol reverses the Warburg effect
PFK↓, leading to increased PDH activity, inhibiting HK and PFK, and downregulating PKM2 activity

2331- RES,    Resveratrol improves follicular development of PCOS rats via regulating glycolysis pathway and targeting SIRT1
- in-vivo, Nor, NA
*LDHA↑, resveratrol treatment significantly increased the expression of LDH-A, PKM2, and SIRT1 in the ovarian tissues of PCOS rats
*PKM2↑,
*SIRT1↑,
*Glycolysis↝, protective effects of resveratrol in the PCOS rats may be associated with the regulation of glycolysis-related mediators including PKM2, LDH-A, and SIRT1.

2441- RES,    Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions
- Review, Var, NA
*toxicity↓, Although resveratrol at high doses up to 5 g has been reported to be non-toxic [34], in some clinical trials, resveratrol at daily doses of 2.5–5 g induced mild-to-moderate gastrointestinal symptoms [
*BioAv↝, After an oral dose of 25 mg in healthy human subjects, the concentrations of native resveratrol (40 nM) and total resveratrol (about 2 µM) in plasma suggested significantly greater bioavailability of resveratrol metabolites than native resveratrol
*Dose↝, The total plasma concentration of resveratrol did not exceed 10 µM following high oral doses of 2–5 g
*hepatoP↑, hepatoprotective effects
*neuroP↑, neuroprotective properties
*AntiAg↑, Resveratrol possesses the ability to impede platelet aggregation
*COX2↓, suppresses promotion by inhibiting cyclooxygenase-2 activity
*antiOx↑, It is widely recognized that resveratrol has antioxidant properties at concentrations ranging from 5 to 10 μM.
*ROS↓, antioxidant properties at concentrations ranging from 5 to 10 μM.
*ROS↑, pro-oxidant properties when present in doses ranging from 10 to 40 μM
PI3K↓, It is known that resveratrol suppresses PI3-kinase, AKT, and NF-κB signaling pathways [75] and may affect tumor growth via other mechanisms as well
Akt↓,
NF-kB↓,
Wnt↓, esveratrol inhibited breast cancer stem-like cells in vitro and in vivo by suppressing Wnt/β-catenin signaling pathway
β-catenin/ZEB1↓,
NRF2↑, Resveratrol activated the Nrf2 signaling pathway, causing separation of the Nrf2–Keap1 complex [84], leading to enhanced transcription of antioxidant enzymes, such as glutathione peroxidase-2 [85] and heme-oxygenase (HO-1)
GPx↑,
HO-1↑,
BioEnh?, Resveratrol was demonstrated to have an impact on drug bioavailability,
PTEN↑, Resveratrol could suppress leukemia cell proliferation and induce apoptosis due to increased expression of PTEN
ChemoSen↑, Resveratrol enhances the sensitivity of cancer cells to chemotherapeutic agents through various mechanisms, such as promoting drug absorption by tumor cells
eff↑, it can also be used in nanomedicines in combination with various compounds or drugs, such as curcumin [101], quercetin [102], paclitaxel [103], docetaxel [104], 5-fluorouracil [105], and small interfering ribonucleic acids (siRNAs)
mt-ROS↑, enhancing the oxidative stress within the mitochondria of these cells, leading to cell damage and death.
Warburg↓, Resveratrol Counteracts Warburg Effect
Glycolysis↓, demonstrated in several studies that resveratrol inhibits glycolysis through the PI3K/Akt/mTOR signaling pathway in human cancer cells
GlucoseCon↓, resveratrol reduced glucose uptake by cancer cells due to targeting carrier Glut1
GLUT1↓,
lactateProd↓, therefore, less lactate was produced
HK2↓, Resveratrol (100 µM for 48–72 h) had a negative impact on hexokinase II (HK2)-mediated glycolysis
EGFR↓, activation of EGFR and downstream kinases Akt and ERK1/2 was observed to diminish upon exposure to resveratrol
cMyc↓, resveratrol suppressed the expression of leptin and c-Myc while increasing the level of vascular endothelial growth factor.
ROS↝, it acts as an antioxidant in regular conditions but as a strong pro-oxidant in cancer cells,
MMPs↓, Main targets of resveratrol in tumor cells. COX-2—cyclooxygenase-2, SIRT-1—sirtuin 1, MMPs—matrix metalloproteinases,
MMP7↓, Resveratrol was shown to exert an inhibitory effect on the expression of β-catenins and also target genes c-Myc, MMP-7, and survivin in multiple myeloma cells, thus reducing the proliferation, migration, and invasion of cancer cells
survivin↓,
TumCP↓,
TumCMig↓,
TumCI↓,

2440- RES,    Resveratrol inhibits Hexokinases II mediated glycolysis in non-small cell lung cancer via targeting Akt signaling pathway
- in-vitro, Lung, H460 - in-vivo, Lung, NA - in-vitro, Lung, H1650 - in-vitro, Lung, HCC827
AntiTum↑, profound anti-tumor effect on human non-small cell lung cancer (NSCLC) via regulation of glycolysis
Glycolysis↓,
HK2↓, Resveratrol impaired hexokinase II (HK2)-mediated glycolysis,
EGFR↓, Exposure to resveratrol decreased EGFR and downstream kinases Akt and ERK1/2 activation
Akt↓,
ERK↓,
GlucoseCon↓, figure 2
lactateProd↓, figure 2
TumCG↓, Resveratrol inhibits tumor growth and HK2 expression in a xenograft mouse model
Ki-67↓, Ki-67 and HK2 were significantly suppressed in the resveratrol treated group compared with the vehicle treated group

2439- RES,    By reducing hexokinase 2, resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice
- in-vitro, HCC, HCCLM3 - in-vitro, Nor, L02 - in-vitro, HCC, SMMC-7721 cell - in-vitro, HCC, Bel-7402 - in-vitro, HCC, HUH7
HK2↓, The induction of mitochondrial apoptosis was associated with the decrease of HK2 expression by resveratrol in HCC cells
ChemoSen↑, In addition, resveratrol enhanced sorafenib induced cell growth inhibition in aerobic glycolytic HCC cells.
other↑, HCC cell lines show an increased rate of aerobic glycolysis compared to healthy cells.
Glycolysis↓, resveratrol suppresses aerobic glycolysis in several cancers, including breast and ovarian cancers
lactateProd↓, Our data showed that resveratrol (20 μM) treatment of HCC-LM3 cells significantly decreased the concentration of lactate in the cell culture
TumCP↓, Resveratrol inhibits proliferation and induces apoptosis partly by suppressing HCC glycolysis
Casp3↑, significant upregulation of active caspase-3 and cleaved PARP in HCC-LM3 cells treated with 40 μM of resveratrol
cl‑PARP↑,
PKM2↓, dose of 40 μM, resveratrol downregulated the protein expression of PKM2 in HCC-LM3 and Bel-7402 cells

3055- RES,    Resveratrol and Tumor Microenvironment: Mechanistic Basis and Therapeutic Targets
- Review, Var, NA
BioAv↓, Resveratrol is poorly bioavailable, and that considered the major hindrance to exert its therapeutic effect, especially for cancer management
BioAv↓, at lower doses (25 mg per healthy subject) demonstrate that the mean proportion of free resveratrol in plasma was 1.7–1.9% with a mean plasma concentration of free resveratrol around 20 nM
Dose↑, Boocock and his colleagues studied the pharmacokinetic of resveratrol; in vitro data showed that minimum of 5 µmol/L resveratrol is essential for the chemopreventive effects to be elicited
eff↑, Despite the low bioavailability of resveratrol, it shows efficacy in vivo. This may be due to the conversion of both glucuronides and sulfate back to resveratrol in target organs such as the liver
eff↑, repeated administration of high doses of resveratrol generates a higher plasma concentration of parent and a much higher concentration of sulfate and glucuronide conjugates in the plasma
Dose↑, The doses tested in this study were 0.5, 1.0, 2.5 or 5.0 g daily for 29 days. No toxicity was detected, but moderate gastrointestinal symptoms were reported for 2.5 and 5.0 g doses
BioAv↑, the co-administration of piperine with resveratrol was used to enhance resveratrol bioavailability
ROS↑, Recent studies have shown that resveratrol increases ROS generation and decreases mitochondrial membrane potential
MMP↓,
P21↑, treatment decreased the viability of melanoma cells by activating the expression of both p21 and p27, which promoted cell cycle arrest.
p27↑,
TumCCA↑,
ChemoSen↑, Additionally, the use of resveratrol with cisplatin in malignant human mesothelioma cells (MSTO-211H and H-2452 cells) synergistically induces cell death by increasing the intracellular ROS level [64].
COX2↓, covers the down-regulation of the products of the following genes, COX-2, 5-LOX, VEGF, IL-1, IL-6, IL-8, AR and PSA [93].
5LO↓,
VEGF↓,
IL1↓,
IL6↓,
IL8↓,
AR↓,
PSA↓,
MAPK↓, by preventing also the activation of the MAPK and PI3K/Akt signaling pathways, it suppresses HIF-1a and VEGF release in ovarian cancer cells of humans
Hif1a↓,
Glycolysis↓, Resveratrol was found to effectively impede the activation, invasion, migration and glycolysis of PSCs induced by reactive oxygen species (ROS) by down-regulating the expression of microRNA 21 (miR-21)
miR-21↓,
PTEN↑, also by increasing the phosphatise and tensin homolog (PTEN) protein levels
Half-Life↝, 25 mg/70 kg resveratrol administered to healthy human participants, the compound predominantly appeared in the form of glucuronide and sulfate conjugates in serum and urine and reached its peak concentrations in serum about 30 min after ingestion
*IGF-1↓, Brown and colleagues noted how a major decline in circulating insulin-like growth factor (IGF)-I as well as IGF-binding proteins (IGFBP-3) among healthy individuals can be credited to the intake of resveratrol
*IGFBP3↑,
Half-Life↓, Microactive® and Resveratrol SR and manufactured by Bioactives. This compound is capable of sustained release for over 12 h to increase intestinal residence time.

3026- RosA,    Modulatory Effect of Rosmarinic Acid on H2O2-Induced Adaptive Glycolytic Response in Dermal Fibroblasts
- in-vitro, Nor, NA
*ROS↓, H2O2 caused a significant ROS increase in the cells, and pre-treatment with rosmarinic acid (5–50 µM) decreased ROS significantly in the presence of glutathione
*ATP↑, The rosmarinic acid also recovered intracellular ATP and decreased NADPH production via the pentose phosphate pathway.
*NADPH↓,
*HK2↓, (HK-2), phosphofructokinase-2 (PFK-2), and lactate dehydrogenase A (LDHA), were downregulated in cells treated with rosmarinic acid
*PFK2↓,
*LDHA↓,
*GSR↑, GSR), glutathione peroxidase-1 (GPx-1), and peroxiredoxin-1 (Prx-1) and redox protein thioredoxin-1 (Trx-1) were upregulated in treated cells compared to control cells.
*GPx↑,
*Prx↑,
*Trx↑,
*antiOx↑, To sum up, the rosmarinic acid could be used as an antioxidant against H2O2-induced adaptive responses in fibroblasts by modulating glucose metabolism, glycolytic genes, and GSH production.
*GSH↑, The pre-treatment of rosmarinic acid could raise intracellular GSH to protect cells from ROS
*ROS↓, rosmarinic acid pre-treatment reduced the amount of ROS in the fibroblasts upon the addition of H2O2
*GlucoseCon↓, both compounds also decreased glucose consumption and lactate production
*lactateProd↓,
*Glycolysis↝, The results indicated that rosmarinic acid is able to shape cellular glucose utilization, glycolysis, and GSH.
*ATP↑, The rosmarinic acid also recovered intracellular ATP and decreased NADPH production via the pentose phosphate pathway.
*NADPH↓,
*PPP↓,

3036- RosA,    Anti-Warburg effect of rosmarinic acid via miR-155 in colorectal carcinoma cells
- in-vitro, CRC, HCT8 - in-vitro, CRC, HCT116 - in-vitro, CRC, LS174T
GlucoseCon↓, RA suppressed glucose consumption and lactate generation in colorectal carcinoma cells;
lactateProd↓,
Hif1a↓, RA inhibited the expression of transcription factor hypoxia-inducible factor-1α (HIF-1α) that affects the glycolytic pathway.
Inflam↓, RA could not only repress proinflammatory cytokines using enzyme-linked immunosorbent assay but it could also suppress microRNAs related to inflammation by real-time PCR
miR-155↓, MiR-155 induces the Warburg effect and is reversed by RA
STAT3↓, RA could inhibit the expression of transcription factor STAT3, and it suppressed the phosphorylation of STAT3
Glycolysis↓, Meanwhile, RA inhibited the expression of transcription factor HIF-1α that affected the glycolytic pathway
IL6↓, RA could significantly regulate miR-155 and in turn alter the IL-6/STAT3 signaling, resulting in the inhibition of inflammation in the tumor micro environment and the eventual anti-Warburg effect
Warburg↓,

3935- RT,    Sodium rutin ameliorates Alzheimer's disease-like pathology by enhancing microglial amyloid-β clearance
- in-vivo, AD, NA
*Aβ↓, rutin enhances microglial Aβ clearance, providing a potential therapeutic avenue for Alzheimer’s disease treatment.
*Glycolysis↓, NaR promotes a metabolic switch from anaerobic glycolysis to mitochondrial OXPHOS (oxidative phosphorylation), which could provide microglia with sufficient energy (ATP) for Aβ clearance.
*OXPHOS↑,
*memory↑, eventually reversing spatial learning and memory deficits. Our findings suggest that NaR is a potential therapeutic agent for AD.
*BioAv↓, poor solubility in aqueous media (approximately 0.125 g/liter at room temperature) has largely limited its usage owing to its poor bioavailability
*BioAv↑, In the present study, we processed rutin into sodium salt [hereafter called sodium rutin (NaR)], which is highly water soluble and bioavailable.
*cognitive↑, NaR ameliorates learning and memory deficits and rescues synaptic impairment in mouse models of AD
*Inflam↓, NaR decreases neuroinflammation in AD mice

4906- Sal,    A Concise Review of Prodigious Salinomycin and Its Derivatives Effective in Treatment of Breast Cancer: (2012–2022)
- Review, BC, NA
CSCs↓, Salinomycin (SAL), a polyether ionophore antibiotic being used in the poultry industry, was identified as a powerful anti-cancer compound that possesses broad-spectrum activities, especially against CSCs.
Casp3↑, SAL has been shown to affect the mitochondria, leading to caspase-3 cleaving poly-ADP ribose polymerase (PARP), resulting in apoptosis.
cl‑PARP↝,
Apoptosis↑,
ROS↑, SAL has shown the ability to affect prostate cancer (PC-3) cell lines through the production of reactive oxygen species (ROS), leading to programmed cell death.
ABC↓, potential use of SAL as an ABC transporter inhibitor
OXPHOS↓, Inhibition of Oxidative Phosphorylation and Glycolysis
Glycolysis↓,
eff↑, SAL in combination with glucose analogs (2-DG, 2-FDG) increased the toxicity of SAL towards cancer cells and showed that cancer cells are dependent on glycolysis for ATP production
TumAuto↑, Induction of Autophagy, ROS, and DNA Damage
DNAdam↑,
Wnt↓, Inhibition of the Wnt Signaling Cascade
Ferritin↓, SAL was tested, and at 0.5 μM iron accumulation in the lysosome, a reduction in iron keeper ferritin expression and elevated iron regulatory protein-2 (IRP2) were observed
Iron↑, a novel mechanism of action of SAL affecting breast CSCs is iron accumulation in the lysosome. and an increased amount of iron in the lysosome produces ROS, which leads to apoptosis

3195- SFN,    AKT1/HK2 Axis-mediated Glucose Metabolism: A Novel Therapeutic Target of Sulforaphane in Bladder Cancer
- in-vitro, Bladder, UMUC3
ATP↓, SFN strongly downregulates ATP production by inhibiting glycolysis and mitochondrial oxidative phosphorylation (OXPHOS).
Glycolysis↓,
OXPHOS↓,
HK2↓, SFN weaken the glycolytic flux by suppressing multiple metabolic enzymes, including hexokinase 2 (HK2) and pyruvate dehydrogenase (PDH).
PDH↓,
AKT1↓, SFN decreases the level of AKT1 and p-AKT ser473 , especially in low-invasive UMUC3 cells.
p‑Akt↓,

2404- SFN,    Prostate cancer chemoprevention by sulforaphane in a preclinical mouse model is associated with inhibition of fatty acid metabolism
- in-vitro, Pca, LNCaP - in-vitro, Pca, 22Rv1 - in-vivo, NA, NA
ACC1↓, SFN (5 and 10 μM) resulted in downregulation of protein and mRNA levels of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN), but not ATP citrate lyase
FASN↓,
CPT1A↓, SFN decreased ACC1, FASN and CPT1A expression in LNCaP and 22Rv1 cells
β-oxidation↓, SFN treatment decreased expression of β-oxidation dehydrogenases
SREBP1?, SFN treatment decreased SREBP1 protein level in prostate cancer cells
HK2↓, Similarly, when Hi-Myc mice were given 1 mg/mouse of sulforaphane three times each week for 5–10 weeks, expression of HKII, PKM2 and LDHA was significantly decreased.
PKM2↓,
LDHA↓,
Glycolysis↓, These results provide evidence that sulforaphane suppresses in vivo glycolysis in prostate cancer cells

2405- SFN,    Sulforaphane Targets the TBX15/KIF2C Pathway to Repress Glycolysis and Cell Proliferation in Gastric Carcinoma Cells
- in-vitro, GC, SGC-7901 - in-vitro, GC, BGC-823
TumCP↓, Sulforaphane can reduce cell proliferation and PKM2-mediated glycolysis in gastric carcinoma cells, apparently by activating the TBX15/KIF2C pathway.
Glycolysis↓,
TBX15↑,
GlucoseCon↓, Overexpressing TBX15 in SGC7901 and BGC823 cells significantly reduced glucose uptake, lactate production, cell viability, expression of KIF2C, and pyruvate kinase M2-mediated (PKM2) glycolysis. These effects were recapitulated by treatment with sulf
lactateProd↓,
tumCV↓,
PKM2↓,
KIF2C↓,

2403- SFN,    Reversal of the Warburg phenomenon in chemoprevention of prostate cancer by sulforaphane
- in-vitro, Pca, LNCaP - in-vitro, Pca, 22Rv1 - in-vitro, Pca, PC3 - in-vivo, NA, NA
ECAR↓, SFN treatment: (i) decreased real-time extracellular acidification rate in LNCaP, but not in PC-3 cell line;
HK2↓, (ii) significantly downregulated expression of hexokinase II (HKII), pyruvate kinase M2 and/or lactate dehydrogenase A (LDHA) in vitro in cells and in vivo . HKII: 32%
PKM2↓, PKM2: 45%
LDHA↓, LDHA: 33%
Glycolysis↓, (iii) significantly suppressed glycolysis in prostate of Hi-Myc mice
Warburg↓, Reversal of the Warburg phenomenon

2406- SFN,    Sulforaphane and Its Protective Role in Prostate Cancer: A Mechanistic Approach
- Review, Pca, NA
HK2↓, When TRAMP mice were given 6 μmol/mouse (1 mg/mouse) three times a week for 17–19 weeks, the prostate tumor expression of glycolysis-promoting enzymes such as (HKII), 2 (PKM2) and (LDHA) was decreased by 32–45%
PKM2↓,
LDHA↓,
Glycolysis↓, These results provide evidence that sulforaphane suppresses in vivo glycolysis in prostate cancer cells
LAMP2↑, The study shows that 10–20 μM of sulforaphane significantly increased lysosome-associated membrane protein 2 (LAMP2) in the cell lines
Hif1a↓, sulforaphane has been shown to suppress HIF-1α
DNAdam↓, SFN causes DNA damage and prevents DNA repair in prostate cancer cell
DNArepair↓,
Dose↝, 5 to 100 mg/kg of sulforaphane reduce tumors in animal models [ 5 , 19]. For a 70 kg human, this translates to 350–7000 mg/kg, which is significantly above the upper threshold of tolerable doses

2446- SFN,  CAP,    The Molecular Effects of Sulforaphane and Capsaicin on Metabolism upon Androgen and Tip60 Activation of Androgen Receptor
- in-vitro, Pca, LNCaP
AR↓, Sulforaphane and capsaicin decreased nuclear AR, prostate specific antigen and Bcl-XL levels, and cell proliferation induced by androgen and Tip60 in LNCaP cells.
Bcl-xL↓,
TumCP↓,
Glycolysis↓, Sulforaphane at 10 µM reduced the glycolysis and glycolytic capacity by 42% and 39%,
HK2↓, These bioactive compounds prevented the increase in glycolysis, hexokinase and pyruvate kinase activity, and reduced HIF-1α stabilization induced by androgen and Tip60 in LNCaP cells.
PKA↓,
Hif1a↓, Sulforaphane and Capsaicin Reduced the Increased HIF-1α Levels Induced by Androgen Stimulus and Tip60 Overexpression
PSA↓, Sulforaphane and capsaicin prevented the activation of AR signaling (decreased nuclear AR levels and PSA levels)
ECAR↓, and glycolysis (decreased EACR; and HK and PK activities) induced by androgen and Tip60.
BioAv↑, increased sulforaphane bioavailability can be attained after the intake of sulforaphane-enriched broccoli sprout preparation (generated by quick steaming followed by myrosinase treatment) in mice
BioAv↓, Liposomal and methoxypoly (ethylene glycol)-poly(ε-caprolactone) microencapsulation increase capsaicin bioavailability by 3.34-fold and 6-fold respectively in rats
*toxicity↓, considering that the minimum lethal oral dose of capsaicin is 100 mg/Kg body weight in mice, its consumption could be safely increased

2448- SFN,    Sulforaphane and bladder cancer: a potential novel antitumor compound
- Review, Bladder, NA
Apoptosis↑, Recent studies have demonstrated that Sulforaphane not only induces apoptosis and cell cycle arrest in BC cells, but also inhibits the growth, invasion, and metastasis of BC cells
TumCG↓,
TumCI↓,
TumMeta↓,
glucoNG↓, Additionally, it can inhibit BC gluconeogenesis
ChemoSen↑, demonstrate definite effects when combined with chemotherapeutic drugs/carcinogens.
TumCCA↑, SFN can block the cell cycle in G2/M phase, upregulate the expression of Caspase3/7 and PARP cleavage, and downregulate the expression of Survivin, EGFR and HER2/neu
Casp3↑,
Casp7↑,
cl‑PARP↑,
survivin↓,
EGFR↓,
HER2/EBBR2↓,
ATP↓, SFN inhibits the production of ATP by inhibiting glycolysis and mitochondrial oxidative phosphorylation in BC cells in a dose-dependent manner
Glycolysis↓,
mt-OXPHOS↓,
AKT1↓, dysregulation of glucose metabolism by inhibiting the AKT1-HK2 axis
HK2↓,
Hif1a↓, Sulforaphane inhibits glycolysis by down-regulating hypoxia-induced HIF-1α
ROS↑, SFN can upregulate ROS production and Nrf2 activity
NRF2↑,
EMT↓, inhibiting EMT process through Cox-2/MMP-2, 9/ ZEB1 and Snail and miR-200c/ZEB1 pathways
COX2↓,
MMP2↓,
MMP9↓,
Zeb1↓,
Snail↓,
HDAC↓, FN modulates the histone status in BC cells by regulating specific HDAC and HATs,
HATs↓,
MMP↓, SFN upregulates ROS production, induces mitochondrial oxidative damage, mitochondrial membrane potential depolarization, cytochrome c release
Cyt‑c↓,
Shh↓, SFN significantly lowers the expression of key components of the SHH pathway (Shh, Smo, and Gli1) and inhibits tumor sphere formation, thereby suppressing the stemness of cancer cells
Smo↓,
Gli1↓,
BioAv↝, SFN is unstable in aqueous solutions and at high temperatures, sensitive to oxygen, heat and alkaline conditions, with a decrease in quantity of 20% after cooking, 36% after frying, and 88% after boiling
BioAv↝, It has been reported that the ability of individuals to use gut myrosinase to convert glucoraphanin into SFN varies widely
Dose↝, Excitingly, it has been reported that daily oral administration of 200 μM SFN in melanoma patients can achieve plasma levels of 655 ng/mL with good tolerance

1452- SFN,    Sulforaphane Suppresses the Nicotine-Induced Expression of the Matrix Metalloproteinase-9 via Inhibiting ROS-Mediated AP-1 and NF-κB Signaling in Human Gastric Cancer Cells
- in-vitro, GC, AGS
MMP9↓, Sulforaphane effectively suppressed ROS, p38 MAPK, Erk1/2, AP-1, and NF-κB activation by inhibiting MMP-9 expression in gastric cancer AGS cells.
p38↓,
ERK↓,
AP-1↓,
ROS↓, results indicate that sulforaphane suppressed the nicotine-induced MMP-9 via regulating ROS generation in human gastric cancer AGS cells ( by Inhibiting ROS Generation)
NF-kB↓, Sulforaphane Suppresses Nicotine-Induced MMP-9 Expression by Inhibiting Reporter Activities of AP-1 and NF-κB
TumCI↓,
MMP9↓, Suppressing MMP-9 Expression
HDAC↓, Rutz et al. reported that sulforaphane acts as a histone deacetylase (HDAC) inhibitor to prostate cancer cell progression
Glycolysis↓, sulforaphane decreased glycolytic metabolism in a hypoxia microenvironment by inhibiting hypoxia-induced HIF-1α
Hif1a↓,
*memory↑, Sulforaphane could prevent memory dysfunction and improve cognitive function
*cognitive↑,

1484- SFN,    Sulforaphane’s Multifaceted Potential: From Neuroprotection to Anticancer Action
- Review, Var, NA - Review, AD, NA
neuroP↑, current evidence supporting the neuroprotective and anticancer effects of SFN
AntiCan↑,
NRF2↑, neuroprotective effects through the activation of the Nrf2 pathway
HDAC↓, histone deacetylase was inhibited after human subjects ingested 68 g of broccoli sprouts
eff↑, sensitize cancer cells to chemotherapy
*ROS↓, protecting neurons [14] and microglia [15] against oxidative stress
neuroP↑, neuroprotective effects in Alzheimer’s disease (AD)
HDAC↓, capacity as a histone deacetylase (HDAC) inhibitor
*toxicity∅, normal cells are relatively resistant to SFN-induced cell death
BioAv↑, SFN has good bioavailability; it can reach high intracellular and plasma concentrations
eff↓, However, it is important to consider that at lower doses, specifically 2.5 μM, SFN resulted in a slight increase in cell proliferation by 5.18–11.84% within a 6 to 48 h treatment window
cycD1/CCND1↓, in breast cancer
CDK4↓, in breast cancer
p‑RB1↓, in breast cancer
Glycolysis↓, in prostate cancer
miR-30a-5p↑, ovarian cancer
TumCCA↑, gastric cancer
TumCG↓,
TumMeta↓,
eff↑, SFN emerged as a critical enhancer of ST’s efficacy by suppressing resistance in RCC cells, offering a potent approach to overcome ST monotherapy limitations.
ChemoSen↑, SFN may improve the effectiveness of chemotherapy by increasing cancer cell sensitivity to the drugs used to treat them
RadioS↑, SFN may help protect healthy cells and tissues from the harmful effects of radiation
CardioT↓, Several studies have demonstrated the protective role of SFN in cardiotoxicity
angioG↓, In colon cancers, SFN blocks cells’ progression and angiogenesis by inhibiting HIF-1α and VEGF expression
Hif1a↓,
VEGF↓,
*BioAv?, SFN is well absorbed in the intestine, with an absolute bioavailability of approximately 82%.
*Half-Life∅, In rats, after an oral dose of 50 μmol of SFN, the plasma concentration of SFN can peak at 20 μM at 4 h and decline with a half-life of about 2.2 h

1481- SFN,  docx,    Combination of Low-Dose Sulforaphane and Docetaxel on Mitochondrial Function and Metabolic Reprogramming in Prostate Cancer Cell Lines
- in-vitro, Pca, LNCaP - in-vitro, Pca, PC3
ChemoSen↑, SFN:DCT combination reduced cell viability to 50%
Casp3↑,
ROS↑, see figure 4
Casp8↑,
Cyt‑c↑, see figure 4
Glycolysis↓, see figure 4
GSH↓, see figure 4
GSH/GSSG↓, GSH/GSSG
*toxicity↓, SFN:DCT combination, administered at reduced doses, not only preserves efficacy but also minimizes toxicity

1734- SFN,    Sulforaphane Inhibits Nonmuscle Invasive Bladder Cancer Cells Proliferation through Suppression of HIF-1α-Mediated Glycolysis in Hypoxia
- in-vitro, Bladder, RT112
selectivity↑, sulforaphane, a natural chemical which was abundant in cruciferous vegetables, could suppress bladder cancer cells proliferation in hypoxia significantly stronger than in normoxia
TumCP↓,
Glycolysis↓, sulforaphane decreased glycolytic metabolism in a hypoxia microenvironment by downregulating hypoxia-induced HIF-1α and blocking HIF-1α t
Hif1a↓,

2410- SIL,    Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF
- in-vitro, GBM, U87MG - in-vitro, GBM, U251 - in-vivo, NA, NA
TumAuto↑, Mechanistically, silibinin activates autophagy through depleting ATP by suppressing glycolysis.
ATP↓,
Glycolysis↓, Silibinin suppressed glycolysis in glioma cells
H2O2↑, Then, autophagy improves intracellular H2O2 via promoting p53-mediated depletion of GSH and cysteine and downregulation of xCT
P53↑,
GSH↓,
xCT↓,
BNIP3↝, The increased H2O2 promotes silibinin-induced BNIP3 upregulation and translocation to mitochondria
MMP↑, silibinin-induced mitochondrial depolarization, accumulation of mitochondrial superoxide
mt-ROS↑,
mtDam↑, Autophagy contributed to silibinin-induced mitochondria damage
HK2↓, protein levels of HK II, PFKP, and PKM2 were all downregulated time-dependently by silibinin in U87, U251, SHG-44, and C6 glioma cells
PFKP↓,
PKM2↓, silibinin suppressed glycolysis via downregulation of HK II, PFKP, and PKM2.
TumCG↓, Silibinin inhibited glioma cell growth in vivo

1140- SIL,    Silibinin-mediated metabolic reprogramming attenuates pancreatic cancer-induced cachexia and tumor growth
- in-vitro, PC, AsPC-1 - in-vivo, PC, NA - in-vitro, PC, MIA PaCa-2 - in-vitro, PC, PANC1 - in-vitro, PC, Bxpc-3
TumCG↓,
Glycolysis↓,
cMyc↓,
STAT3↓,
TumCP↓,
Weight∅, prevents the loss of body weight and muscle.
Strength↑,
DNAdam↑,
Casp3↑,
Casp9↑,
GLUT1↓,
HK2↓,
LDHA↓,
GlucoseCon↓, silibinin inhibits glucose uptake and lactate release
lactateProd↓,
PPP↓, significant reduction in pentose phosphate pathway (PPP) metabolites, including 6-phosphogluconate (~50%), erythrose-4-phosphate (~40%), sedoheptulose-7-phosphate and sedoheptulose bis-phosphate (~ 70%)
Ki-67↓, reduced Ki67-positive cells
p‑STAT3↓,
cachexia↓,

1001- SIL,    Silibinin down-regulates PD-L1 expression in nasopharyngeal carcinoma by interfering with tumor cell glycolytic metabolism
- in-vitro, NA, NA
TumCG↓,
Glycolysis↓, Silibinin potently inhibits tumor growth and promotes a shift from aerobic glycolysis toward oxidative phosphorylation.
OXPHOS↑,
LDHA↓,
lactateProd↓,
i-citrate↑,
Hif1a↓,
PD-L1↓, silibinin can alter PD-L1 expression by interfering with HIF-1α/LDH-A

2359- SK,    Regulating lactate-related immunometabolism and EMT reversal for colorectal cancer liver metastases using shikonin targeted delivery
- in-vivo, Liver, NA
TumCG↓, SHK@HA-MPDA achieved tumor-targeted delivery via hyaluronic acid-mediated binding with the tumor-associated CD44, and efficiently arrested colorectal tumor growth
PKM2↓, The inhibition of PKM2 by SHK@HA-MPDA led to the remodeling of the tumor immune microenvironment
EMT↓, reversing EMT by lactate abatement and the suppression of TGFβ signaling
TGF-β↓,
Glycolysis↓, EMT reversal by suppressing glycolysis and lactate production
lactateProd↓,
ATP↓, SHK@HA-MPDA nanosystem efficiently inhibited tetramer PKM2 and further reduced lactate and ATP production

2419- SK,    Regulation of glycolysis and the Warburg effect in wound healing
- in-vivo, Nor, NA
Glycolysis↓, Treatment with 5–10 μM of the glycolysis inhibitor shikonin significantly decreased gene expression of the facilitative glucose transporters, GLUT1 and GLUT3
GLUT1↓,
GLUT3↓,
HK2↓, shikonin downregulated expression of the rate-limiting enzymes HK1 and HK2, although a 20 μM dose was needed
HK1↓, HK1
PFK1↓, Shikonin treatment also downregulated the rate-limiting enzyme PFK1
PFK2↓, PFK2 expression was only significantly lowered with a 20 μM dose
PKM2↓, 5 μM shikonin treatment inhibits gene expression of PKM2 (8.59 vs. 2.30, P < 0.001) and downregulated PDK1
lactateProd↓, coupled with decreased lactate production at higher concentrations of shikonin (10 μM and 20 μM)
GlucoseCon↓, shikonin effectively downregulated key enzymes involved in glucose uptake, glycolysis, and lactate production

2418- SK,    Experimental Study of Hepatocellular Carcinoma Treatment by Shikonin Through Regulating PKM2
- in-vitro, HCC, SMMC-7721 cell - in-vitro, HCC, HUH7 - in-vitro, HCC, HepG2
tumCV↓, The results of CCK-8 showed that shikonin significantly inhibited cell viability of HCC cells.
GlucoseCon↓, The levels of glucose uptake and lactate production were dramatically decreased by shikonin-treated.
lactateProd↓,
ChemoSen↑, shikonin enhanced the anti-cancer effect of sorafenib in vitro and in vivo.
PKM2↓, By inhibiting PKM2, shikonin inhibited proliferation and glycolysis and induced cell apoptosis in HCC cells.
Glycolysis↓,

2415- SK,    Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways
- in-vivo, Arthritis, NA
Apoptosis?, shikonin induced apoptosis and autophagy in RA-FLSs by activating the production of reactive oxygen species (ROS) and inhibiting intracellular ATP levels, glycolysis-related proteins, and the PI3K-AKT-mTOR signaling pathway.
TumAuto↑,
ROS↑,
ATP↓,
Glycolysis↓, shikonin can inhibit RA-glycolysis in FLSs
PI3K↓,
Akt↓,
mTOR↓,
*Apoptosis↓, Shikonin can significantly reduce the expression of apoptosis-related proteins, paw swelling in rat arthritic tissues, and the levels of inflammatory factors in peripheral blood, such as TNF-α, IL-6, IL-8, IL-10, IL-17A, and IL-1β while showing less
*Inflam↓,
*TNF-α↓,
*IL6↓,
*IL8↓,
*IL10↓,
*IL17↓,
*hepatoP↑, while showing less toxicity to the liver and kidney.
*RenoP↑,
PKM2↓, The expression of glycogen proteins PKM2, GLUT1, and HK2 decreased with increasing concentrations of shikonin
GLUT1↓,
HK2↓,

2370- SK,    The role of pyruvate kinase M2 in anticancer therapeutic treatments
- Review, Var, NA
Glycolysis↓, In summary, shikonin is able to inhibit tumor growth by suppressing aerobic glycolysis, which is mediated by PKM2 in vivo
PKM2↓,
EGFR↓, another study indicated that shikonin reduced epidermal growth factor receptor, PI3K, p-AKT, Hypoxia inducible factor-1α (HIF-1α) and PKM2 expression levels
PI3K↓,
p‑Akt↓,
Hif1a↓,

2356- SK,    ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment
- in-vitro, Ovarian, CaOV3 - in-vitro, Ovarian, OV90 - in-vivo, NA, NA
PKM2↓, Shikonin effectively inhibits the molecular interaction between ESM1 and PKM2, consequently preventing the formation of PKM2 dimers and thereby inhibiting ovarian cancer glycolysis, fatty acid synthesis and vasculogenic mimicry.
Glycolysis↓, Shikonin inhibited glycolysis in OV90 cells
FASN↓,
lactateProd↓, In both CAOV3 and OV90 cells, the levels of lactic acid were significantly reduced in the ESM1 and Shikonin group when compared to the ESM1-overexpressing group
Warburg↓, Shikonin could repress the interaction between PKM2 and ESM1 and the formation of PKM2 dimers to attenuate OC migration and invasion and VM by driving the Warburg effect in vitro.
TumCG↓, Shikonin itself significantly inhibited tumor growth
VM↓, Shikonin significantly attenuates the OC growth and the VM of OC cells

2357- SK,    GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism
- Study, HCC, NA - in-vivo, NA, NA
AntiTum↑, Shikonin exerted a remarkable antitumor effect in many tumors.
GTPBP4↓, We found that, first Shikonin could inhibit the binding of GTPBP4 and PKM2 proteins
PKM2↓,
lactateProd↓, increased lactate production and glucose consumption activity by GTPBP4 overexpression in PLC/PRF/5 and SMMC-7721 cells cells could be fully antagonized by Shikonin
GlucoseCon↓,
Glycolysis↓, Shikonin could suppress HCC growth and glycolysis through inhibiting PKM2 dependent glucose metabolism
E-cadherin↑, Downregulation of E-cadherin in GTPBP4 overexpression PLC/PRF/51 xenografts was also rescued by Shikonin treatment
TumCG↓, We found that Shikonin administration efficiently suppresses tumor growth in orthotopic xenograft mouse models of HCC

2362- SK,    RIP1 and RIP3 contribute to shikonin-induced glycolysis suppression in glioma cells via increase of intracellular hydrogen peroxide
- in-vitro, GBM, U87MG - in-vivo, GBM, NA - in-vitro, GBM, U251
RIP1↑, we found shikonin activated RIP1 and RIP3 in glioma cells in vitro and in vivo, which was accompanied with glycolysis suppression
RIP3↑,
Glycolysis↓,
G6PD↓, shikonin-induced decreases of glucose-6-phosphate and pyruvate and downregulation of HK II and PKM2
HK2↓,
PKM2↓,
H2O2↑, shikonin also triggered accumulation of intracellular H2O2 and depletion of GSH and cysteine
GSH↓,
ROS↑, It was documented that inhibition of HK II with its inhibitor 3-bromopyruvate or knockdown of its level resulted in accumulation of ROS

2200- SK,    Shikonin inhibits the growth of anaplastic thyroid carcinoma cells by promoting ferroptosis and inhibiting glycolysis
- in-vitro, Thyroid, CAL-62 - in-vitro, Thyroid, 8505C
NF-kB↓, SKN inhibits the expression of NF-κB,GPX4,TXNRD1,PKM2,GLUT1.
GPx4↓,
TrxR1↓, TXNRD1
PKM2↓,
GLUT1↓,
Glycolysis↓, inhibiting glycolysis in ATC cells.
Ferroptosis↑, SKN in inducing intracellular ferroptosis
GlucoseCon↓, Measurements of glucose uptake after 1, 3, and 5 μM concentrations of SKN treatment for 24 h showed a decrease in both cells
lactateProd↓, Lactate production in the cells decreased with the rise of SKN treatment concentration
ROS↑, cellular ROS increased significantly with the rise in SKN concentration

2196- SK,    Research progress in mechanism of anticancer action of shikonin targeting reactive oxygen species
- Review, Var, NA
*ALAT↓, shikonin was found to mitigate the rise in ALT and AST levels triggered by LPS/GalN
*AST↓,
*Inflam?, demonstrated the anti-inflammatory properties of shikonin within two traditional mouse models frequently employed in pharmacological research to assess anti-inflammatory activities
*EMT↑, Shikonin stimulates EMT by weakening the nuclear translocation of NF-κB p65
ROS?, naphthoquinone framework possesses the capacity to produce ROS, which in turn modulate cellular oxidative stress levels
TrxR1↓, Duan and colleagues demonstrated that shikonin specifically inhibits the physiological function of TrxR1 by targeting its Sec residue
PERK↑, In vivo Western blot of HCT-15(colon cancer) xenografts showed shikonin upregulated PERK/eIF2α/ATF4/CHOP and IRE1α/JNK pathways.
eIF2α↑,
ATF4↑,
CHOP↑,
IRE1↑,
JNK↑,
eff↝, oral shikonin did not demonstrate anti-tumor effects in the colorectal cancer model, intraperitoneal injection significantly inhibited tumor growth.
DR5↑, upregulation of Death Receptor 5 (DR5) in cholangiocarcinoma cells through ROS-induced activation of the JNK signaling cascade.
Glycolysis↓, inhibited glycolysis in HepG2 cells by suppressing the activity of PKM2, a critical enzyme within the glycolytic pathway
PKM2↓,
ChemoSen↑, The combination of shikonin with drugs can reverse drug resistance and enhance therapeutic efficacy
GPx4↓, shikonin conjunction with cisplatin overcame drug resistance in cancer cells, downregulated GPX4, and upregulated haemoglobin oxygenase 1 (HMOX1) inducing iron death in cells.
HO-1↑,

2192- SK,    Shikonin Inhibits Tumor Growth of ESCC by suppressing PKM2 mediated Aerobic Glycolysis and STAT3 Phosphorylation
- in-vitro, ESCC, KYSE-510 - in-vitro, ESCC, Eca109 - in-vivo, NA, NA
TumCP↓, Shikonin effectively inhibited cell proliferation in dose-dependent and time-dependent manner compared with the control group
Glycolysis↓, detection of glycolysis showed that Shikonin suppressed the glucose consumption, lactate production, glycolytic intermediates and pyruvate kinase enzymatic activity.
GlucoseCon↓,
lactateProd↓,
PKM2↓,
p‑PKM2↓, decreased the expression of p-PKM2 and p-STAT3 in vivo
p‑STAT3↓,
GLUT1↓, Shikonin suppressed the expression of GLUT1 and HK2 proteins which are related to glycolysis.
HK2↓,
TumW↓, tumor weight in the Shikonin group decreased by approximately 40% compared with the vehicle control group,

2187- SK,  VitK3,    Shikonin, vitamin K3 and vitamin K5 inhibit multiple glycolytic enzymes in MCF-7 cells
- in-vitro, BC, MCF-7
Glycolysis↓, naphthaquinones, including shikonin, vitamin K3 and vitamin K5, have been proven to decrease the rate of glycolysis in cancer cells, which is partly due to suppressed pyruvate kinase activity.
PKM2↓,

2186- SK,    Shikonin differentially regulates glucose metabolism via PKM2 and HIF1α to overcome apoptosis in a refractory HCC cell line
- in-vitro, HCC, HepG2 - in-vitro, HCC, HCCLM3
Glycolysis↓, shikonin treatment has been reported to inhibit glycolysis by suppressing the activity of pyruvate kinase M2 (PKM2) and to induce apoptosis by increasing reactive oxygen species (ROS) production.
PKM2↓,
Apoptosis↑,
ROS↑,
OXPHOS⇅, Shikonin up-regulated mitochondrial biogenesis to increase mitochondrial oxidative phosphorylation in HepG2 cells, but displayed the opposite trend in HCCLM3 cells.
eff↓, insensitivity of HCCLM3 cells to shikonin treatment.

2185- SK,    Shikonin Inhibits Tumor Growth in Mice by Suppressing Pyruvate Kinase M2-mediated Aerobic Glycolysis
- in-vitro, Lung, LLC1 - in-vitro, Melanoma, B16-BL6 - in-vivo, NA, NA
Glycolysis↓, confirming the inhibitory effect of shikonin on tumor aerobic glycolysis
GlucoseCon↓, shikonin dose-dependently inhibited glucose uptake and lactate production in Lewis lung carcinoma (LLC) and B16 melanoma cells
lactateProd↓,
PKM2↓, suppression of cell aerobic glycolysis by shikonin is through decreasing PKM2 activity
selectivity↑, shikonin treatment significantly promoted tumor cell apoptosis compared to untreated control cells.
Warburg↓, agreement with previous findings of shikonin as a Warburg effect inhibitor
TumVol↓, A significant reduction of tumor size (Fig. 7B) and weight (Fig. 7C) was observed when shikonin was injected at concentration of 1 or 10 mg/kg.
TumW↓,

2182- SK,  Cisplatin,    Shikonin inhibited glycolysis and sensitized cisplatin treatment in non-small cell lung cancer cells via the exosomal pyruvate kinase M2 pathway
- in-vitro, Lung, A549 - in-vitro, Lung, PC9 - in-vivo, NA, NA
tumCV↓, shikonin inhibited the viability, proliferation, invasion, and migration of NSCLC cells A549 and PC9, and induced apoptosis.
TumCP↓,
TumCI↓,
TumCMig↓,
Apoptosis↑,
PKM2↓, As the inhibitor of pyruvate kinase M2 (PKM2), a key enzyme in glycolysis, shikonin inhibited glucose uptake and the production of lactate
Glycolysis↓,
GlucoseCon↓,
lactateProd↓,
ChemoSen↑, In vivo chemotherapeutic assay showed that shikonin reduced the tumor volume and weight in NSCLC mice model and increased the sensitivity to cisplatin chemotherapy.
TumVol↓,
TumW↓,
GLUT1↓, combination of shikonin and cisplatin downregulated the expression of PKM2 and its transcriptionally regulated downstream gene glucose transporter 1 (Glut1) in tumor tissue

2181- SK,    Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2
- in-vitro, BC, MCF-7 - in-vitro, Lung, A549 - in-vitro, Cerv, HeLa
Glycolysis↓, Shikonin and alkannin significantly inhibited the glycolytic rate, as manifested by cellular lactate production and glucose consumption in drug-sensitive and resistant cancer cell lines
lactateProd↓,
GlucoseCon↓,
PKM2↓, shikonin and alkannin are the most potent and specific inhibitors to PKM2 reported so far
LDH∅, LDH was not inhibited by shikonin, alkannin and the analogs

3045- SK,    Cutting off the fuel supply to calcium pumps in pancreatic cancer cells: role of pyruvate kinase-M2 (PKM2)
- in-vitro, PC, MIA PaCa-2
ECAR↓, Shikonin caused a concentration- and time-dependent inhibition of ECAR, which was more effective in highly glycolytic cells cultured in high-glucose (25 mM, Fig. 3ci) vs glucose-restricted cells (5 mM, Fig. 3cii).
Glycolysis↓, Collectively, these data suggest that shikonin exerts its cytotoxicity by inhibiting glycolysis and inducing ATP depletion, most likely due to inhibition of PKM2.
ATP↓, Only the highest concentration of shikonin (5 µM) induced a significant ATP depletion between 15 min and 6 h
PKM2↓,
TumCMig↓, Shikonin reduces PDAC cell migration
Ca+2↑, Shikonin induces cytotoxic Ca2+ overload
GlucoseCon↓, shikonin inhibited glucose consumption and lactate production with an IC50 of 5–10 μM in MCF-7 cells that exclusively express PKM2
lactateProd↓,
MMP↓, Shikonin is also reported to impair mitochondrial function and increase oxidative stress
ROS↑,

3041- SK,    Promising Nanomedicines of Shikonin for Cancer Therapy
- Review, Var, NA
Glycolysis↓, SHK could regulate immunosuppressive tumor microenvironment through inhibiting glycolysis of tumor cells and repolarizing tumor-associated macrophages (TAMs).
TAMS↝,
BioAv↓, HK is a hydrophobic natural molecule with unsatisfactory solubility, rapid intestinal absorption, obvious “first pass” effect, and rapid clearance, leading to low oral bioavailability.
Half-Life↝, SHK displays a half-life of 15.15 ± 1.41 h and Cmax of 0.94 ± 0.11 μg/ml in rats when administered intravenously.
P21↑, Table 1
ERK↓,
ROS↑,
GSH↓,
MMP↓,
TrxR↓,
MMP13↓,
MMP2↓,
MMP9↓,
SIRT2↑,
Hif1a↓,
PKM2↓,
TumCP↓, Inhibit Cell Proliferation
TumMeta↓, Inhibit Cells Metastasis and Invasion
TumCI↓,

2470- SK,    PKM2/PDK1 dual-targeted shikonin derivatives restore the sensitivity of EGFR-mutated NSCLC cells to gefitinib by remodeling glucose metabolism
- in-vitro, Lung, H1299
PKM2↓, Base on this, we designed a series of novel shikonin (SK) thioether derivatives as PKM2/PDK1 dual-target agents, among which the most potent compound E5 featuring a 2-methyl substitution on the benzene ring exerted significantly increased inhibitory
PDK1↓,
Glycolysis↓, E5 could significantly inhibit the proliferation and aerobic glycolysis of NSCLC cell

2125- TQ,    Thymoquinone Selectively Kills Hypoxic Renal Cancer Cells by Suppressing HIF-1α-Mediated Glycolysis
- in-vitro, RCC, RCC4 - in-vitro, RCC, Caki-1
Hif1a↓, TQ reduced HIF-1α protein levels in renal cancer cells. In addition, decreased HIF-1α levels in both cytoplasm and nucleus after treatment with 10 μM of TQ were observed in Caki-1 cells
eff↝, suggesting that suppression of HIF-1α by TQ may be connected to Hsp90-mediated HIF-1α stabilization
uPAR↓, significantly downregulated the hypoxia-induced tumor promoting HIF-1α target genes, such as FN1, LOXL2, uPAR, VEGF, CA-IX, PDK1, GLUT1, and LDHA, in TQ-treated Caki-1
VEGF↓,
CAIX↓,
PDK1↓,
GLUT1↓,
LDHA↓,
Glycolysis↓, we found that TQ significantly increases glucose levels in hypoxic Caki-1 and A498 cultured medium, indicating that hypoxia-induced anaerobic glycolysis is significantly suppressed by TQ treatment
e-lactateProd↓, Consistent with suppression of hypoxic glycolysis by TQ treatment, increased extracellular lactate levels under hypoxia were decreased in TQ-treated Caki-1 and A498 renal cancer cells
i-ATP↓, intracellular ATP levels were significantly decreased in TQ-treated Caki-1 and A498 cells under hypoxia

3431- TQ,    PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW48
Glycolysis↓, we provide evidence that thymoquinone inhibits glycolytic metabolism (Warburg effect) in colorectal cancer cell lines.
Warburg↓,
HK2↓, was due, at least in part, to the inhibition of the rate-limiting glycolytic enzyme, Hexokinase 2 (HK2),
ATP↓, such reduction in glucose fermentation capacity also led to a significant reduction in overall ATP production as well as maintaining the redox state (NADPH production) of these cells
NADPH↓, showed a significant reduction in glucose fermentation, ATP and NADPH production rates
PI3K↓, reduction in HK2 levels upon TQ treatment coincided with significant inhibition in PI3K-AKT activation
Akt↓,
TumCP↓, Thymoquinone Inhibits Cell Migration and Invasion via Modulating Glucose Metabolic Reprogramming
E-cadherin↑, TQ was able to induce E-cadherin while inhibiting N-cadherin expression
N-cadherin↓,
Hif1a↓, TQ is reported to induce cell death in renal cell carcinoma [81] and pancreatic cancers [82] via inhibiting HIF1α and pyruvate kinase M2 (PKM2)-mediated glycolysis
PKM2↓,
GlucoseCon↓, TQ treatment inhibited the glucose uptake and subsequent lactate production in HCT116 and SW480 cells
lactateProd↓,
EMT↓, TQ inhibits cell proliferation, clonogenicity and epithelial-mesenchymal transition (EMT) in CRC cells (HCT116 and SW480)

2454- Trip,    Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ
- in-vitro, HNSCC, HaCaT - in-vivo, NA, NA
GSDME-N↑, Triptolide eliminates head and neck cancer cells through inducing gasdermin E (GSDME) mediated pyroptosis.
Pyro↑,
cMyc↓, TPL treatment suppresses expression of c-myc and mitochondrial hexokinase II (HK-II) in cancer cells
HK2↓,
BAD↑, leading to activation of the BAD/BAX-caspase 3 cascade and cleavage of GSDME by active caspase 3.
BAX↑,
Casp3↑,
NRF2↓, TPL treatment suppresses NRF2/SLC7A11 (also known as xCT) axis
xCT↓,
ROS↑, and induces reactive oxygen species (ROS) accumulation, regardless of the status of GSDME.
eff↑, Combination of TPL with erastin, an inhibitor of SLC7A11, exerts robust synergistic effect in suppression of tumor survival in vitro and in a nude mice model.
Glycolysis↓, TPL treatment repressed c-Myc/HK-II axis and aerobic glycolysis in head and neck cancer cells
GlucoseCon↓, as evidenced by reduced glucose consumption, lactate production and cellular ATP content following TPL treatment
lactateProd↓,
ATP↓,
xCT↓, TPL (50 nM) treatment decreased the protein levels of NRF2 and SLC7A11 (
eff↑, combination of TPL with erastin is a promising strategy for head and neck cancer therapy.

2413- TTT,    Tumor treating fields (TTFields) impairs aberrant glycolysis in glioblastoma as evaluated by [18F]DASA-23, a non-invasive probe of pyruvate kinase M2 (PKM2) expression
- in-vitro, GBM, U87MG
PKM2↓, Quantitative Western blot analysis and qualitative immunofluorescence for PKM2 confirmed the TTFields-induced reduction in PKM2 expression. TTFields exposure reduced PKM2 expression by 49% at 3 d
Glycolysis↓, Regardless, both outcomes suggest a shift from aberrant glycolysis towards oxidative phosphorylation
OXPHOS↑,

2350- UA,    Ursolic acid-mediated changes in glycolytic pathway promote cytotoxic autophagy and apoptosis in phenotypically different breast cancer cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Akt↓, UA (20 µM) also diminished AKT signaling that affected glycolysis as judged by decreased levels of HK2, PKM2, ATP and lactate.
Glycolysis↓,
HK2↓,
PKM2↓,
ATP↓, 20 µM UA caused a decrease in intracellular ATP and lactate pools
lactateProd↓,
AMPK↑, UA-induced energy stress activated AMPK that resulted in cytotoxic autophagy and apoptosis
TumAuto↑,
Apoptosis↑,
ERK↓, UA-promoted apoptosis was associated with decreased pERK1/2 signals and the depolarization of mitochondrial membrane potential.
MMP↓,
NO↑, 20 µM UA treatment resulted in an increase in nitric oxide levels
ROS↑, UA-induced elevation in total reactive oxygen species (ROS), total superoxide and mitochondrial superoxide production was more potent than BA-mediated oxidative stress
DNAdam↑, UA and BA promoted DNA breaks,

942- UA,    Ursolic Acid Inhibits Breast Cancer Metastasis by Suppressing Glycolytic Metabolism via Activating SP1/Caveolin-1 Signaling
- vitro+vivo, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Cav1↑, may impair the glycolytic metabolism of breast cancer cells by activating Caveolin-1 (Cav-1)
Glycolysis↓, Ursolic Acid Impairs the Glycolytic Metabolism
cMyc↓, ursolic acid (1~30 μM) treatment significantly attenuated the protein expression levels of both the glycolysis-related proteins (c-Myc and LDH-A)
LDHA↓,
Nrf1↓, and the mitochondrial respiration-related proteins (Nrf1 and PGC-1α)
PGC-1α↓,
Sp1/3/4↑, Mechanistically, ursolic acid could activate SP1-mediated CAV1 transcription by promoting SP1 expression
TumCG↓,

5021- UA,    Anticancer effect of ursolic acid via mitochondria-dependent pathways
- Review, Var, NA
Inflam↓, anti-inflammatory effect of UA was linked to attenuation of production of proinflammatory cytokines including tumor necrosis factor α, interleukin (IL)-6 and/or IL-17 (
TNF-α↓,
IL6↓,
IL17↓,
NF-kB↓, UA was associated with suppression of the nuclear factor-κB (NF-κβ) pathway, inhibition of expression of cyclooxygenase-2 (COX-2)
COX2↓,
*AntiDiabetic↑, UA demonstrated an antidiabetic functio
*hepatoP↑, UA can provide hepatoprotective activity against several liver diseases
ALAT↓, UA reduced the serum/plasma levels of alanine transaminase and aspartate transaminase, which are liver disease biomarkers
AST↓,
TumCP↓, UA inhibited tumorigenesis and cancer cell proliferation, modulated apoptosis and cell cycle progression and promoted autophagy
Apoptosis↑,
TumCCA↑,
TumAuto↑,
tumCV↓, UA inhibited the viability and migration of T47D, MCF-7 and MDA-MB-231 breast cancer cells by targeting phosphoinositide-3-kinase/protein kinase B (PI3K/Akt)
TumCMig↓,
Glycolysis↓, Additionally, UA affected glycolysis. The effect was accompanied by decreased levels of ATP, lactate, hexokinase 2 and pyruvate kinase. I
ATP↓,
lactateProd↓,
HK2↓, The Akt inhibition affected glycolysis and markedly decreased levels of HK2, pyruvate kinase M2, ATP and lactate.
PKA↓,
COX2↓, UA may down-regulate the expression of COX-2
mtDam↑, UA significantly enhanced proapoptotic effects and stimulated mitochondrial dysfunction by activating caspases 3, 8 and 9, and downregulated Bcl-2 expression in these cancer cells.
Casp3↑,
Casp8↑,
Casp9↑,
Akt↓, UA downregulated the Akt signaling in three breast cancer cell lines
ROS↑, Derivative 17 significantly increased the production of ROS for 24 h, while 5 and 23 did so for 48 h.
MMP↓, human breast cancer cell line MDA-MB-231, UA decreased the mitochondrial ∆Ψm,
P53↑, regulatory proteins p53 and Bax were upregulated while the antiapoptotic protein Bcl-2 was downregulated following treatment with UA.

5022- UA,    Ursolic Acid’s Alluring Journey: One Triterpenoid vs. Cancer Hallmarks
- Review, Var, NA
TumCP↓, inhibition of cell proliferation, induction of apoptosis, suppression of angiogenesis, inhibition of metastasis, and modulation of the tumor microenvironment
Apoptosis↑,
angioG↑,
TumMeta↓,
BioAv↓, acknowledges hurdles related to UA’s low bioavailability,
Hif1a↓, graphical abstract
Glycolysis↓,
mitResp↓,
Akt↓,
MAPK↓,
ERK↓,
mTOR↓,
P53↑,
P21↑,
E2Fs↑,
STAT3↓,
MMP↓,
NLRP3↓,
iNOS↓,
CHK1↓,
Chk2↓,
BRCA1↓,
E-cadherin↑,
N-cadherin↓,
Casp↑,
p62↓,
LC3II↑,
Vim↓,
ROS↑, administration of UA has effectively modulated the generation of both cellular and mitochondrial ROS
CSCs↓, This, in turn, triggers a response in embryonic CSCs known as DNA damage response (DDR), strongly suggesting the potential for UA-induced cell death
DNAdam↑,
GutMicro↑, UA has shown potential in modulating the composition of the gut microbiota and improving the microenvironment within the digestive system
VEGF↓, UA treatment significantly reduced the expression of VEGF-A and FGF-β in both CRC tumors and HT-29 cells (

3140- VitC,    Vitamin-C-dependent downregulation of the citrate metabolism pathway potentiates pancreatic ductal adenocarcinoma growth arrest
- in-vitro, PC, MIA PaCa-2 - in-vitro, Nor, HEK293
citrate↓, pharmacological doses of vitamin C are capable of exerting an inhibitory action on the activity of CS, reducing glucose-derived citrate levels
FASN↓, Moreover, ascorbate targets citrate metabolism towards the de novo lipogenesis pathway, impairing fatty acid synthase (FASN) and ATP citrate lyase (ACLY) expression.
ACLY↓,
LDH↓, correlated with a remarkable decrease in extracellular pH through inhibition of lactate dehydrogenase (LDH) and overall reduced glycolytic metabolism.
Glycolysis↓,
Warburg↓, Dismissed citrate metabolism correlated with reduced Warburg effectors such as the pyruvate dehydrogenase kinase 1 (PDK1) and the glucose transporter 1 (GLUT1),
PDK1↓,
GLUT1↓,
LDHA↓, Reduced LDHA expression was also observed after vitamin C exposure, leading to a vast extracellular acidification rate (ECAR) reduction.
ECAR↓,
PDH↑, enhancing PDH activity
eff↑, Surprisingly, an impressive 85% of tumor growth inhibition is described in the combinatory treatment of vitamin C and gemcitabine in our preclinical PDAC PDX model

3141- VitC,    High-dose Vitamin C inhibits PD-L1 expression by activating AMPK in colorectal cancer
- in-vitro, CRC, HCT116
Glycolysis↓, Vitamin C inhibits immune evasion by regulating glycolysis
eff↑, VitC suppresses tumor growth and enhances immunotherapy in combination with anti-PD-L1
PD-L1↓, We found that VitC inhibits aerobic glycolysis in HCT116 cells while also downregulating PD-L1 expression.
AMPK↑, VitC's activation of AMPK, which downregulates HK2 and NF-κB, ultimately resulting in reduced PD-L1 expression and increased T cell infiltration.
HK2↓,
NF-kB↓,
Warburg↓, Our research shows that high-dose VitC downregulating the Warburg effect, suppressing CRC growth
tumCV↓, After treatment with VitC, the cell viability of HCT116 cells significantly decreased
GLUT1↓, marked reduction in the mRNA level of glycolysis-related proteins GLUT1, PKM2, and LDHA
PKM2↓,
LDHA↓,
CD4+↑, Our research shows that high-dose VitC increases CD4+ and CD8+ T cell infiltration in tumor tissues by inhibiting PD-L1
CD8+↑,

3143- VitC,  ATO,    Vitamin C enhances the sensitivity of osteosarcoma to arsenic trioxide via inhibiting aerobic glycolysis
- in-vitro, OS, NA
TumCP↓, synthetic application of vitamin C (VitC, 800 μM) and ATO (1 μM) significantly further inhibited the proliferation, migration, and invasion of OS cells and promoted cell apoptosis in vitro.
TumCMig↓,
TumCI↓,
eff↑, synthetic application of vitamin C (VitC, 800 μM) and ATO (1 μM) significantly further inhibited the proliferation,
Glycolysis↓, VitC and ATO directly suppresses the aerobic glycolysis of OS cells with the decreased production of pyruvate, lactate, and ATP via inhibiting the expression of the critical glycolytic genes (PGK1, PGM1, and LDHA).
lactateProd↓,
ATP↓,
PGK1↓,
PGM1↓,
LDHA↓,

3145- VitC,    Vitamin C inhibits the growth of colorectal cancer cell HCT116 and reverses the glucose‐induced oncogenic effect by downregulating the Warburg effect
- in-vitro, CRC, HCT116
Warburg↓, Notably, as a potential Warburg effect inhibitor, VC suppressed cancer growth in a concentration-dependent manner and further reversed the glucose-induced oncogenic effect.
TumCG↓,
Glycolysis↓,
GlucoseCon↓, 1 h-exposure to 5 mM VC led to an almost 50% reduction in glucose consumption, ATP and lactate contents in cancer cells, with mild impact on normal cells
ATP↓,
lactateProd↓,
selectivity↑, Meanwhile, normal cell had little apparent change
GLUT1↓, (GLUT1, PKM2, and LDHA) were significantly decreased, with p-AMPK/AMPK increased and p-mTOR/mTOR decreased, consistent with the cytotoxicity on 3 kinds of cancer cells
PKM2↓,
LDHA↓,
mTOR↓,

3107- VitC,    Repurposing Vitamin C for Cancer Treatment: Focus on Targeting the Tumor Microenvironment
- Review, Var, NA
Risk↓, VitC supplementation resulted in dose-dependent reductions in all-cause mortality and the risk of various cancers
*ROS↓, Vitamin C (VitC) at the physiological dose (μM) is known to exhibit antioxidant properties.
ROS↑, However, it functions as a prooxidant at the pharmacological dose (mM) achieved by intravenous administration.
VEGF↓, VitC suppressed tumor angiogenesis in colon cancer-bearing mice by downregulating the expression and secretion of VEGF-A and VEGF-D
COX2↓, VitC impairs COX-2 activity and inhibits VEGF mRNA expression in melanoma cells in a time-dependent manner
ER Stress↑, VitC increases the ER stress-mediated breast cancer apoptosis via activation of the IRE-JNK-CHOP signaling pathway, an effect independent of ROS
IRE1↑,
JNK↑,
CHOP↑,
Hif1a↓, On the one hand, VitC directly inhibits HIF-1α-mediated glycolysis-related genes expression and the downstream acidic metabolites
eff↑, ROS generated by VitC treatment exerts a synergistic effect with other glycolysis inhibitors, providing a combined therapeutic strategy
Glycolysis↓,
MMPs↓, VitC inhibits a variety of metalloproteinases (MMPs) mRNA, which degrade ECM and release growth factors that drive tumor metastasis
TumMeta↓,
YAP/TEAD↓, VitC treatment reduces YAP1 expression while upregulating SYNPO-2; therefore, inhibiting metastasis of TNBC
eff↑, VitC enhances the killing efficiency of Hep G2 cells by low-dose sorafenib in vitro.
TET1↑, VitC stimulation of TET2 activity in the renal cell carcinoma

4468- VitC,  SSE,    Selenium modulates cancer cell response to pharmacologic ascorbate
- in-vivo, GBM, U87MG - in-vitro, CRC, HCT116
eff↓, In vivo, dietary selenium deficiency resulted in significant enhancement of ascorbate activity against glioblastoma xenografts
TumCD↑, pharmacologic ascorbate raises the serum ascorbate concentration into the millimolar range, a concentration at which ascorbate has been shown to kill cancer cells in vitro
ChemoSen↑, Pharmacologic ascorbate has been shown to synergize with multiple chemotherapeutic agents in animal models and is well-tolerated in human patients [1,4], motivating ongoing clinical trials.
ROS⇅, Indeed, the role of ascorbate as either a pro- or anti-oxidant has been suggested to depend on concentration, with low doses mitigating ROS and high doses generating them
DNAdam↑, H2O2 generation by ascorbate has been associated with DNA damage and subsequent PARP activation, which can deplete NAD and thereby inhibit glycolysis
PARP↑,
NAD↓,
Glycolysis↓,
Fenton↑, Ascorbate cytotoxicity depends on the intracellular labile iron pool (Fig 1a) [3,9]. One explanation for this phenomenon is that ascorbate-generated H2O2 causes toxicity through Fenton chemistry
lipid-P↑, extensive lipid peroxidation
eff↓, More generally, they establish dietary selenium depletion as a potential means of sensitizing tumors to free radical stress.
H2O2↑, High concentrations (mM) of ascorbate have been shown to generate H2O2 in vitro
other↝, Selenium supplementation has been shown to protect cells against iron-dependent cell death by supporting increased expression of selenoproteins, including GPX4, which defend against oxidative stress

2366- VitD3,    Vitamin D3 decreases glycolysis and invasiveness, and increases cellular stiffness in breast cancer cells
- in-vitro, BC, MCF-7
Glycolysis↓, We find that VD3 treatment significantly down-regulates glycolytic enzymes and genes and decreases glucose uptake - for both lowly metastatic MCF-7 and highly metastatic MDA-MB-231 (MB231) breast cancer cells.
tumCV↓, VD3 also significantly decreases cell viability by inducing apoptosis
Apoptosis↑,
mTOR↓, consistent with decreased expression of mammalian target of rapamycin (mTOR),
AMPK↑, increases 5' adenosine monophosphate-activated protein kinase (AMPK) activation
EMT↓, presumably a consequence of reversal of the epithelial to mesenchymal transition
E-cadherin↑, increased E-cadherin, and F-actin, and reduced vimentin expression
F-actin↑,
Vim↓,

2369- VitD3,    Long Non-coding RNA MEG3 Activated by Vitamin D Suppresses Glycolysis in Colorectal Cancer via Promoting c-Myc Degradation
- in-vitro, CRC, DLD1 - in-vitro, CRC, RKO
MEG3↑, MEG3 can be activated by vitamin D and vitamin D receptor (VDR).
Glycolysis↓, overexpression of MEG3 significantly inhibited glycolysis
lactateProd↓, as well as lactate production in CRC cells
LDHA↓, inhibited c-Myc target genes involved in the glycolysis pathway such as lactate dehydrogenase A
PKM2↓, pyruvate kinase muscle 2, and hexokinase 2
HK2↓,

2367- VitD3,    Vitamin D activates FBP1 to block the Warburg effect and modulate blast metabolism in acute myeloid leukemia
- in-vivo, AML, NA
FBP1↑, VD3-induced FBP1 overexpression might be a novel therapeutic target to block the “Warburg Effect” to reduce energy production in AML blasts.
Warburg↓,
Glycolysis↓,
lactateProd↓, functional lactate assay showed the significant reduction of the lactate concentration in MV4–11 cells after 1,25VD3 treatment

2365- VitD3,    Vitamin D Affects the Warburg Effect and Stemness Maintenance of Non- Small-Cell Lung Cancer Cells by Regulating the PI3K/AKT/mTOR Signaling Pathway
- in-vitro, Lung, A549 - in-vitro, Lung, H1975 - in-vivo, NA, NA
Glycolysis↓, vitamin D inhibited glycolysis and stemness maintenance in A549 and NCI-H1975 cells.
Warburg↓, vitamin D attenuated the expression of metabolism-related enzymes associated with the Warburg effect (GLUT1, LDHA, HK2, and PKM2).
GLUT1↓,
LDHA↓,
HK2↓,
PKM2↓,
OCT4↓, In addition, vitamin D down-regulated the expression of stemness-related genes (Oct-4, SOX-2, and Nanog) and the expression of PI3K, AKT, and mTOR.
SOX2↓,
Nanog↓,
PI3K↓,
Akt↓,
mTOR↓,

1214- VitK2,    Vitamin K2 promotes PI3K/AKT/HIF-1α-mediated glycolysis that leads to AMPK-dependent autophagic cell death in bladder cancer cells
- in-vitro, Bladder, T24/HTB-9 - in-vitro, Bladder, J82
Glycolysis↑, Vitamin K2 renders bladder cancer cells more dependence on glycolysis than TCA cycle
GlucoseCon↑, results suggest that Vitamin K2 is able to induce metabolic stress, including glucose starvation and energy shortage, in bladder cancer cells, upon glucose limitation.
lactateProd↑,
TCA↓, Vitamin K2 promotes glycolysis and inhibits TCA cycle in bladder cancer cells
PI3K↑,
Akt↑,
AMPK↑, Vitamin K2 remarkably activated AMPK pathway
mTORC1↓,
TumAuto↑,
GLUT1↑, Vitamin K2 stepwise elevated the expression of some glycolytic proteins or enzymes, such as GLUT-1, Hexokinase II (HK2), PFKFB2, LDHA and PDHK1, in bladder cancer T24
HK2↑,
LDHA↑, Vitamin K2 stepwise elevated the expression of some glycolytic proteins or enzymes, such as GLUT-1, Hexokinase II (HK2), PFKFB2, LDHA and PDHK1, in bladder cancer T24
ACC↓, Vitamin K2 remarkably decreased the amounts of Acetyl coenzyme A (Acetyl-CoA) in T24 cells
PDH↓, suggesting that Vitamin K2 inactivates PDH
eff↓, Intriguingly, glucose supplementation profoundly abrogated AMPK activation and rescued bladder cancer cells from Vitamin K2-triggered autophagic cell death.
cMyc↓, c-MYC protein level was also significantly reduced in T24 cells following treatment with Vitamin K2 for 18 hours
Hif1a↑, Besides, the increased expression of GLUT-1, HIF-1α, p-AKT and p-AMPK were also detected in Vitamin K2-treated tumor group
p‑Akt↑,
eff↓, 2-DG, 3BP and DCA-induced glycolysis attenuation significantly prevented metabolic stress and rescued bladder cancer cells from Vitamin K2-triggered AMPK-dependent autophagic cell death
eff↓, inhibition of PI3K/AKT and HIF-1α notably attenuated Vitamin K2-upregulated glycolysis, indicating that Vitamin K2 promotes glycolysis in bladder cancer cells via PI3K/AKT and HIF-1α signal pathways.
eff↓, (NAC, a ROS scavenger) not only alleviated Vitamin K2-induced AKT activation and glycolysis promotion, but also significantly suppressed the subsequent AMPK-dependent autophagic cell death.
eff↓, glucose supplementation not only restored c-MYC expression, but also rescued bladder cancer cells from Vitamin K2-triggered AMPK-dependent autophagic cell death
ROS↑, under glucose limited condition, the increased glycolysis inevitably resulted in metabolic stress, which augments ROS accumulation due to lack of glucose for sustained glycolysis.

2301- Wog,    Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
- Review, Var, NA
HK2↓, wogonin was accompanied by decreases in HKII, PDK1, and LDHA expression
PDK1↓,
LDHA↓, Wogonin treatment suppressed LDHA activity in human gastric cancer (SGC-7901) and human lung adenocarcinoma (A549) cells
Hif1a↓, wogonin could reduce HIF-1α expression by inhibiting the PI3K/Akt signaling pathway
PI3K↓,
Akt↓,
Glycolysis↓, suppression of glycolytic-related proteins, and inhibition of PI3K/Akt signaling in vivo
P53↑, Wogonin was found to upregulate p53 and p53-inducible glycolysis in colon cancer (HCT-116), ovarian cancer (A2780), and liver cancer (HepG2) cells
GLUT1↓, also inhibited glycolysis in A2780 xenografts accompanied by the downregulation of GLUT1

2621- Wog,    Natural compounds targeting glycolysis as promising therapeutics for gastric cancer: A review
- Review, Var, NA
Hif1a↓, Wogonin at 15 μg/ml reduces the expression of HIF-1α, and down-regulates the levels of MCT4 and LDH
MCT4↓,
LDH↓,
lactateProd↓, thereby reducing the production of lactic acid,
ECAR↓, improving the acidic microenvironment,
TumCP↓, inhibiting cellular proliferation
Glycolysis↓, Compounds such as wogonin inhibited glycolysis by suppressing HIF-1α

2414- β‐Ele,    Beta‐elemene inhibits breast cancer metastasis through blocking pyruvate kinase M2 dimerization and nuclear translocation
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vivo, NA, NA
TumCMig↓, β‐elemene inhibited breast cancer cell migration, invasion in vitro as well as metastases in vivo
TumCI↓,
TumMeta↓, β‐Elemene inhibited breast cancer metastasis in lung and liver in mice
Glycolysis↓, β‐Elemene further inhibited the process of aerobic glycolysis and decreased the utilization of glucose
GlucoseCon↓,
lactateProd↓, and the production of pyruvate and lactate
PKM2↓, through suppressing pyruvate kinase activity by modulating the transformation of dimeric and tetrameric forms of PKM2.
EGFR↓, blocking PKM2 nuclear translocation and the expression of EGFR, GLUT1 and LDHA by influencing the expression of importin α5
GLUT1↓,
LDHA↓,
ECAR↓, In our research, β‐elemene decreased both ECAR and OCR in MCF‐7 cells, but the cancer cells still survived.
OCR↓,

2425- γ-Toc,    Anticancer Effects of γ-Tocotrienol Are Associated with a Suppression in Aerobic Glycolysis
- in-vitro, NA, MCF-7 - in-vivo, NA, NA
TumCG↓, Treatment with γ-tocotrienol resulted in a dose-responsive inhibition of both +SA and MCF-7 mammary tumor cell growth
GlucoseCon↓, induced a relatively large reduction in glucose utilization, intracellular ATP production and extracellular lactate excretion.
ATP↓,
lactateProd↓,
Glycolysis↓, These effects were also associated with a large decrease in enzyme expression levels involved in regulating aerobic glycolysis
HK2↓, including hexokinase-II, phosphofructokinase, pyruvate kinase M2, and lactate dehydrogenase A
PFK↓,
PKM2↓,
LDHA↓,
Akt↓, γ-Tocotrienol treatment was also associated with a corresponding reduction in the levels of phosphorylated (active) Akt, phosphorylated (active) mTOR, and c-Myc
p‑mTOR↓,
cMyc↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 246

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 1,   Catalase↓, 2,   Catalase↑, 1,   CYP1A1↑, 1,   CYP2E1↑, 1,   Fenton↑, 1,   Ferroptosis↑, 3,   GPx↓, 2,   GPx↑, 2,   GPx4↓, 4,   GSH↓, 19,   GSH/GSSG↓, 1,   GSTP1/GSTπ↝, 1,   GSTs↑, 1,   H2O2↑, 7,   mt-H2O2↑, 1,   HK1↓, 4,   HO-1↓, 2,   HO-1↑, 5,   HO-2↓, 1,   Iron↑, 3,   lipid-P↓, 1,   lipid-P↑, 3,   lipidDe↓, 1,   MDA↑, 2,   NADH↓, 1,   NADPH/NADP+↓, 1,   NQO1↑, 1,   Nrf1↓, 1,   NRF2↓, 3,   NRF2↑, 5,   p‑NRF2↓, 1,   OXPHOS↓, 10,   OXPHOS↑, 12,   OXPHOS⇅, 1,   OXPHOS↝, 1,   mt-OXPHOS↓, 4,   mt-OXPHOS↑, 2,   Prx4↑, 1,   PYCR1↓, 1,   ROS?, 1,   ROS↓, 7,   ROS↑, 85,   ROS⇅, 2,   ROS↝, 1,   i-ROS↑, 1,   mt-ROS↑, 5,   RPM↑, 2,   SIRT3↑, 2,   SOD↓, 3,   SOD↑, 2,   SOD1↑, 1,   SOD2↑, 3,   Thiols↓, 1,   TKT↝, 1,   TrxR↓, 5,   TrxR1↓, 2,   xCT↓, 3,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 2,   FTH1↓, 1,   NCOA4↑, 1,   Zn2+↑, 1,  

Mitochondria & Bioenergetics ⓘ

ADP:ATP↓, 1,   AIF↓, 1,   AIF↑, 4,   ATP↓, 46,   ATP↑, 3,   i-ATP↓, 1,   i-ATP↑, 1,   mt-ATP↓, 1,   CDC2↑, 1,   FGFR1↓, 1,   Insulin↓, 1,   KIF2C↓, 1,   MEK↓, 2,   mitResp↓, 6,   mitResp↑, 3,   MMP↓, 25,   MMP↑, 1,   MPT↑, 1,   mtDam↑, 7,   OCR↓, 11,   OCR↑, 7,   PGC-1α↓, 1,   PGC-1α↑, 2,   Raf↓, 2,   SDH↓, 2,   XIAP↓, 3,  

Core Metabolism/Glycolysis ⓘ

ACC↓, 2,   ACC1↓, 1,   ACLY↓, 4,   ACSL1↓, 1,   adiP↑, 1,   AKT1↓, 3,   ALAT↓, 2,   ALDOA↓, 2,   ALDOAiso2↓, 1,   AminoA↓, 1,   AMPK↑, 14,   p‑AMPK↑, 1,   ATP:AMP↓, 1,   CAIX↓, 3,   Cav1↑, 2,   citrate↓, 2,   i-citrate↑, 1,   cMyc↓, 27,   CPT1A↓, 3,   CYP3A4↓, 1,   ECAR↓, 23,   ECAR↝, 1,   ECAR∅, 1,   ENO1↓, 3,   FAO↓, 2,   FASN↓, 6,   FASN↑, 2,   FBP1↑, 1,   FBPase↑, 3,   G6PD↓, 4,   GAPDH↓, 6,   GDH↓, 1,   GLS↓, 1,   glucoNG↓, 1,   glucoNG↑, 2,   glucose↓, 1,   glucose↑, 1,   GlucoseCon↓, 58,   GlucoseCon↑, 3,   glut↓, 1,   GLUT2↓, 4,   GlutaM↓, 2,   glyC↓, 1,   Glycolysis↓, 223,   Glycolysis↑, 2,   Glycolysis↝, 1,   Glycolysis∅, 1,   HK2↓, 84,   HK2↑, 1,   HK2∅, 1,   IDH1↑, 2,   lact/pyru↓, 1,   lactateProd↓, 75,   lactateProd↑, 1,   e-lactateProd↓, 1,   LDH↓, 17,   LDH↑, 1,   LDH∅, 1,   e-LDH↑, 1,   LDHA↓, 49,   LDHA↑, 1,   LDHA∅, 1,   MCT4↓, 2,   NAD↓, 2,   NADPH↓, 7,   OAA↑, 1,   PDH↓, 8,   PDH↑, 8,   p‑PDH↓, 1,   PDHA1↓, 1,   PDK1?, 2,   PDK1↓, 20,   p‑PDK1↓, 2,   PDK3↓, 1,   PDK3↑, 1,   PDKs↓, 5,   p‑PDKs↓, 1,   PFK↓, 15,   PFK1↓, 8,   PFK2?, 1,   PFK2↓, 3,   PFKP?, 1,   PFKP↓, 3,   PGK1↓, 3,   PGM1↓, 1,   PI3K/Akt↓, 1,   PI3k/Akt/mTOR↓, 1,   PKM1↑, 1,   PKM2↓, 84,   PKM2∅, 1,   p‑PKM2↓, 1,   PKM2:PKM1↓, 2,   PPARγ↓, 1,   PPARγ↑, 2,   PPP↓, 4,   PPP↑, 1,   Pyruv↓, 4,   Pyruv↑, 1,   R5P↝, 1,   p‑S6K↓, 1,   SIRT1↓, 1,   SIRT1↑, 2,   SIRT2↑, 1,   SREBP1?, 1,   TCA↓, 6,   TCA↑, 2,   Warburg↓, 27,   β-oxidation↓, 3,  

Cell Death ⓘ

Akt↓, 38,   Akt↑, 3,   p‑Akt↓, 11,   p‑Akt↑, 1,   Apoptosis?, 3,   Apoptosis↑, 49,   ASK1↑, 1,   BAD↑, 2,   BAX↓, 2,   BAX↑, 10,   Bax:Bcl2↑, 4,   Bcl-2↓, 14,   Bcl-2↑, 1,   Bcl-xL↓, 3,   BIM↑, 2,   Casp↑, 4,   Casp12↑, 1,   Casp2↑, 2,   Casp3↓, 2,   Casp3↑, 29,   cl‑Casp3↑, 3,   proCasp3↓, 1,   Casp7↑, 3,   Casp8↑, 6,   Casp9↑, 13,   cFLIP↓, 1,   Chk2↓, 1,   Cyt‑c↓, 1,   Cyt‑c↑, 16,   Cyt‑c↝, 2,   Diablo↑, 1,   DR4↑, 1,   DR5↑, 4,   Endon↑, 1,   FADD↑, 1,   Fas↑, 2,   Ferroptosis↑, 3,   GSDMC↑, 1,   GSDME-N↑, 1,   hTERT/TERT↓, 2,   iNOS↓, 2,   iNOS↑, 1,   JNK↓, 1,   JNK↑, 4,   MAPK↓, 5,   MAPK↑, 1,   MAPK↝, 1,   Mcl-1↓, 8,   MCT1↓, 1,   MDM2↓, 2,   MEG3↑, 1,   MLKL↑, 1,   Myc↓, 2,   Necroptosis↑, 1,   necrosis↑, 1,   NOXA↑, 1,   p27↑, 4,   p38↓, 1,   p38↑, 3,   PUMA↑, 2,   Pyro↑, 2,   RIP1↑, 1,   p‑RIP1↑, 1,   survivin↓, 7,   Telomerase↓, 3,   TRAIL↑, 1,   TumCD↑, 5,   YAP/TEAD↓, 1,  

Kinase & Signal Transduction ⓘ

CaMKII ↓, 1,   HER2/EBBR2↓, 3,   p‑HER2/EBBR2↓, 1,   PAK↓, 1,   RET↓, 1,   Sp1/3/4↓, 5,   Sp1/3/4↑, 1,  

Transcription & Epigenetics ⓘ

ac‑H4↓, 1,   HATs↓, 1,   miR-145↑, 1,   miR-21↓, 1,   miR-30a-5p↑, 1,   other↓, 1,   other↑, 3,   other↝, 5,   pRB↑, 1,   p‑pRB↓, 1,   TET3↑, 1,   tumCV↓, 17,  

Protein Folding & ER Stress ⓘ

CHOP↑, 9,   eIF2α↓, 1,   eIF2α↑, 3,   p‑eIF2α↑, 3,   ER Stress↑, 11,   GRP78/BiP↑, 5,   HSP70/HSPA5↓, 1,   HSP90↓, 3,   IRE1↑, 2,   PERK↑, 4,   UPR↑, 1,   XBP-1↑, 1,  

Autophagy & Lysosomes ⓘ

ATG3↑, 1,   Beclin-1↑, 2,   BNIP3↝, 1,   LAMP2↑, 2,   LC3‑Ⅱ/LC3‑Ⅰ↑, 2,   LC3B↓, 1,   LC3B-II↑, 2,   LC3II↑, 4,   LC3s↓, 1,   p62↓, 4,   p62↑, 3,   TumAuto↑, 15,  

DNA Damage & Repair ⓘ

BRCA1↓, 1,   CHK1↓, 1,   DNAdam↓, 2,   DNAdam↑, 11,   mt-DNAdam↑, 1,   DNArepair↓, 1,   P53↑, 16,   PARP↓, 2,   PARP↑, 1,   cl‑PARP↑, 9,   cl‑PARP↝, 1,   proPARP↓, 1,   PCNA↓, 4,   SIRT6↑, 1,   TP53↓, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 2,   CDK2↓, 5,   CDK4↓, 7,   Cyc↓, 1,   cycA1/CCNA1↑, 1,   CycB/CCNB1↓, 2,   CycB/CCNB1↑, 1,   cycD1/CCND1↓, 13,   cycD1/CCND1↑, 1,   cycE/CCNE↓, 3,   cycE/CCNE↑, 1,   E2Fs↑, 1,   P21↓, 1,   P21↑, 10,   RB1↓, 1,   p‑RB1↓, 3,   TumCCA↓, 1,   TumCCA↑, 30,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 2,   ALDH1A1↓, 1,   CD133↓, 1,   CD24↓, 1,   CD44↓, 2,   CDK8↓, 1,   CEBPB?, 1,   cFos↓, 1,   cMET↓, 2,   CSCs↓, 8,   Diff↓, 1,   EMT↓, 17,   ERK↓, 14,   ERK↑, 1,   ERK↝, 1,   p‑ERK↓, 1,   p‑FOXO3↓, 1,   Gli1↓, 2,   GSK‐3β↓, 1,   p‑GSK‐3β↓, 1,   GTPBP4↓, 1,   HDAC↓, 7,   HDAC8↓, 1,   HH↓, 1,   IGF-1↓, 3,   IGF-1↝, 1,   IGF-1R↓, 4,   p‑IGF-1R↓, 1,   IGFBP1↑, 1,   Let-7↑, 2,   miR-34a↑, 1,   mTOR↓, 30,   p‑mTOR↓, 4,   mTORC1↓, 1,   p‑mTORC1↓, 1,   n-MYC↓, 1,   Nanog↓, 3,   Nestin↓, 1,   NOTCH↓, 4,   NOTCH1↓, 1,   NOTCH1↑, 2,   OCT4↓, 3,   p‑P70S6K↓, 1,   P90RSK↓, 1,   PI3K↓, 21,   PI3K↑, 1,   PTEN↑, 17,   RAS↓, 2,   Shh↓, 2,   SHP1↑, 1,   Smo↓, 2,   SOX2↓, 5,   STAT1↓, 1,   STAT3↓, 17,   p‑STAT3↓, 8,   STAT5↓, 1,   p‑STAT5↓, 1,   STAT6↓, 2,   TBX15↑, 1,   TOP1↓, 2,   TOP2↓, 2,   TumCG↓, 44,   TumCG↑, 3,   Wnt↓, 5,   Wnt/(β-catenin)↓, 3,   Zn2+↑, 1,  

Migration ⓘ

5LO↓, 2,   AP-1↓, 3,   ATPase↓, 1,   AXL↓, 1,   Ca+2?, 1,   Ca+2↓, 3,   Ca+2↑, 6,   Ca+2↝, 2,   i-Ca+2↓, 1,   i-Ca+2↑, 1,   CAFs/TAFs↓, 1,   E-cadherin↑, 11,   ER-α36↓, 1,   F-actin↑, 1,   FAK↓, 1,   p‑FAK↓, 2,   Furin↓, 1,   ITGB1↓, 1,   ITGB6↓, 1,   Ki-67↓, 7,   MALAT1↓, 1,   miR-155↓, 1,   MMP13↓, 1,   MMP2↓, 13,   MMP3↓, 1,   MMP7↓, 1,   MMP9↓, 16,   MMP9↑, 1,   MMP9:TIMP1↓, 1,   MMPs↓, 6,   N-cadherin↓, 7,   PKA↓, 5,   PKCδ↓, 1,   Rho↓, 1,   RIP3↑, 1,   ROCK1↓, 1,   Slug↓, 4,   SMAD3↓, 1,   Snail?, 1,   Snail↓, 4,   SOX4↑, 1,   SPARC↑, 1,   talin↓, 1,   TET1↑, 2,   TGF-β↓, 3,   TIMP1↓, 2,   TIMP2↓, 1,   Treg lymp↓, 1,   TumCA↑, 1,   TumCI↓, 20,   TumCMig↓, 15,   TumCMig↑, 1,   TumCP↓, 54,   TumMeta↓, 19,   Twist↓, 6,   uPA↓, 5,   uPAR↓, 1,   Vim↓, 7,   Zeb1↓, 2,   ZEB2↓, 1,   ZO-1↑, 1,   α-SMA↓, 1,   α-SMA↑, 1,   β-catenin/ZEB1↓, 9,  

Angiogenesis & Vasculature ⓘ

angioG↓, 17,   angioG↑, 1,   ATF4↑, 3,   ATF4↝, 1,   EGFR↓, 12,   Endoglin↑, 1,   eNOS↑, 1,   EPR↓, 1,   HIF-1↓, 1,   Hif1a↓, 61,   Hif1a↑, 1,   NO↑, 1,   TAMS↝, 1,   VEGF↓, 21,   VEGFR2↓, 4,   VM↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   GLUT1↓, 39,   GLUT1↑, 2,   GLUT3↓, 4,   GLUT3↑, 1,   GLUT4↓, 1,   NHE1↓, 4,   P-gp↓, 3,   SMCT1∅, 1,  

Immune & Inflammatory Signaling ⓘ

CCR7↓, 1,   CD4+↑, 1,   COX1↓, 1,   COX2↓, 12,   CXCR4↓, 3,   HMGB1↓, 1,   ICAM-1↓, 1,   IKKα↓, 1,   IL1↓, 1,   IL1↑, 1,   IL10↓, 3,   IL10↑, 1,   IL17↓, 1,   IL1β↓, 4,   IL2↑, 1,   IL4↓, 2,   IL6↓, 11,   IL8↓, 2,   Inflam↓, 9,   JAK↓, 1,   JAK1↓, 1,   JAK2↓, 5,   pol-M1↑, 1,   M2 MC↓, 2,   pol-M2 MC↓, 1,   MCP1↓, 1,   NF-kB↓, 27,   NF-kB↑, 2,   p‑NF-kB↓, 1,   NK cell↑, 2,   p65↓, 3,   PD-L1↓, 4,   PGE2↓, 2,   PSA↓, 2,   T-Cell↑, 1,   T-Cell↝, 1,   TLR4↓, 1,   TNF-α↓, 4,   TNF-α↑, 1,  

Cellular Microenvironment ⓘ

i-pH↓, 2,  

Protein Aggregation ⓘ

NLRP3↓, 3,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 3,   CDK6↓, 6,  

Drug Metabolism & Resistance ⓘ

ABC↓, 1,   BioAv↓, 11,   BioAv↑, 9,   BioAv↝, 5,   BioEnh?, 1,   BioEnh↑, 1,   ChemoSen↓, 2,   ChemoSen↑, 39,   CYP1A2↑, 1,   CYP2A3/CYP2A6↓, 1,   Dose?, 3,   Dose↓, 3,   Dose↑, 4,   Dose↝, 11,   Dose∅, 6,   eff↓, 23,   eff↑, 82,   eff↝, 6,   Half-Life↓, 3,   Half-Life↝, 3,   MDR1↓, 1,   MRP1↓, 1,   P450↓, 1,   RadioS↑, 19,   selectivity↑, 33,  

Clinical Biomarkers ⓘ

ALAT↓, 2,   AR↓, 3,   AST↓, 2,   BG↓, 2,   BloodF↑, 1,   BRCA1↓, 1,   E6↓, 2,   E7↓, 2,   EGFR↓, 12,   Ferritin↓, 2,   GutMicro↑, 3,   HER2/EBBR2↓, 3,   p‑HER2/EBBR2↓, 1,   hTERT/TERT↓, 2,   IL6↓, 11,   Ki-67↓, 7,   LDH↓, 17,   LDH↑, 1,   LDH∅, 1,   e-LDH↑, 1,   Myc↓, 2,   PD-L1↓, 4,   PSA↓, 2,   TP53↓, 1,   XIST↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 6,   AntiTum↑, 5,   cachexia↓, 1,   cardioP↑, 2,   CardioT↓, 1,   chemoP↓, 1,   ChemoSideEff↓, 3,   hepatoP↓, 1,   neuroP↑, 5,   OS↑, 6,   QoL↑, 2,   radioP↑, 1,   Remission↑, 1,   Risk↓, 2,   Strength↑, 1,   toxicity↓, 7,   toxicity↑, 3,   toxicity↝, 5,   toxicity∅, 1,   TumVol↓, 8,   TumW↓, 8,   Weight∅, 2,  

Infection & Microbiome ⓘ

CD8+↑, 2,  
Total Targets: 612

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 11,   mt-antiOx↑, 1,   Catalase↑, 1,   GPx↑, 2,   GPx1↑, 3,   GPx4↑, 2,   GSH↑, 4,   GSR↑, 1,   HK1↑, 1,   HNE↓, 1,   HO-1↑, 3,   lipid-P↓, 2,   lipidDe↓, 1,   MDA↓, 2,   NADPH/NADP+↑, 1,   NOX4↓, 1,   NQO1↑, 1,   NRF2↑, 4,   OXPHOS↓, 3,   OXPHOS↑, 3,   Prx↑, 1,   ROS↓, 15,   ROS↑, 2,   mt-ROS↓, 2,   mt-ROS↑, 1,   SOD↑, 4,   SOD1↑, 2,   SOD2↑, 1,   Trx↑, 1,  

Metal & Cofactor Biology ⓘ

IronCh↑, 2,  

Mitochondria & Bioenergetics ⓘ

ADP:ATP↓, 1,   ATP↓, 1,   ATP↑, 4,   Insulin↓, 1,   mitResp↓, 1,   MMP↑, 2,   MMP↝, 1,   OCR↓, 1,   OCR↑, 1,   PGC-1α↑, 3,   UCP1↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACC↓, 1,   p‑ACC↑, 1,   ACLY∅, 1,   ALAT↓, 2,   AMPK↑, 1,   p‑AMPK↑, 1,   BMAL1↑, 1,   ECAR↓, 4,   ECAR↑, 1,   ECAR∅, 1,   FAO↑, 2,   FGF21↑, 1,   glucoNG↓, 1,   glucose↓, 1,   GlucoseCon↓, 3,   GlucoseCon↑, 4,   Glycolysis↓, 7,   Glycolysis↑, 10,   Glycolysis↝, 3,   H2S↑, 1,   HK2↓, 4,   HK2↑, 5,   lactateProd↓, 4,   LDHA↓, 2,   LDHA↑, 3,   LDHB↑, 1,   lipidLev↓, 1,   NAD↑, 1,   NADPH↓, 2,   NH3↑, 1,   PDKs↓, 1,   PFK↓, 1,   PFK↑, 1,   PFK1↓, 1,   PFK2↓, 1,   PFKL↑, 2,   PFKM↑, 2,   PFKP↓, 1,   PFKP↑, 1,   PKM2↓, 3,   PKM2↑, 6,   PPARα↑, 2,   PPP↓, 2,   SIRT1↑, 1,   SIRT2↑, 1,   SREBP1↓, 1,   TCA↑, 1,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↓, 2,   MAPK↓, 2,   YAP/TEAD↑, 1,  

Transcription & Epigenetics ⓘ

other?, 1,   other↝, 2,   tumCV↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↑, 1,   ERK↓, 1,   IGF-1↓, 3,   IGFBP3↑, 1,   IGFR↓, 1,   mTOR↓, 2,   PI3K↓, 2,   RAS↓, 1,  

Migration ⓘ

AntiAg↑, 1,   Ca+2↓, 1,   CXCL12↑, 1,   TumCMig↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,   ATF4↑, 1,   Hif1a↓, 1,   Hif1a↑, 2,   Hif1a∅, 1,   VEGF↑, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   GLUT1↑, 2,   GLUT3↑, 1,   GLUT4↑, 3,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CXCL1↓, 1,   IL10↓, 1,   IL17↓, 1,   IL1β↓, 1,   IL2↓, 1,   IL6↓, 2,   IL8↓, 1,   Inflam?, 1,   Inflam↓, 11,   NF-kB↓, 1,   PAR-2↓, 1,   TNF-α↓, 4,  

Cellular Microenvironment ⓘ

pH↑, 1,  

Synaptic & Neurotransmission ⓘ

GABA↝, 1,   tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 3,  

Drug Metabolism & Resistance ⓘ

BioAv?, 1,   BioAv↓, 5,   BioAv↑, 3,   BioAv↝, 2,   BioEnh↑, 1,   Dose↝, 3,   eff↑, 2,   eff↝, 1,   Half-Life↓, 1,   Half-Life↝, 1,   Half-Life∅, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 2,   AST↓, 2,   GutMicro↑, 2,   IL6↓, 2,  

Functional Outcomes ⓘ

AntiAge↑, 3,   AntiCan↓, 1,   AntiDiabetic↑, 1,   cardioP↓, 1,   cardioP↑, 3,   cognitive↑, 6,   hepatoP↑, 8,   memory↑, 4,   motorD↑, 1,   neuroP↑, 9,   OS↑, 1,   RenoP↑, 2,   toxicity↓, 8,   toxicity↑, 1,   toxicity↝, 1,   toxicity∅, 4,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 166

Scientific Paper Hit Count for: Glycolysis, Glycolysis
19 Shikonin
14 3-bromopyruvate
11 Baicalein
11 Sulforaphane (mainly Broccoli)
10 Citric Acid
10 Dichloroacetate
8 EGCG (Epigallocatechin Gallate)
8 Quercetin
8 Resveratrol
7 Berberine
7 Propolis -bee glue
7 Magnetic Fields
6 Artemisinin
6 Vitamin C (Ascorbic Acid)
5 Alpha-Lipoic-Acid
5 Apigenin (mainly Parsley)
5 Ashwagandha(Withaferin A)
5 Betulinic acid
5 Metformin
5 Curcumin
4 Chemotherapy
4 Galloflavin
4 Methylene blue
4 Ursolic acid
4 Vitamin D3
3 2-DeoxyGlucose
3 5-fluorouracil
3 Chrysin
3 diet FMD Fasting Mimicking Diet
3 Honokiol
3 Piperlongumine
3 Silymarin (Milk Thistle) silibinin
2 Radiotherapy/Radiation
2 Capsaicin
2 salinomycin
2 Ellagic acid
2 Emodin
2 Luteolin
2 Oroxylin-A
2 Phenylbutyrate
2 Rosmarinic acid
2 Thymoquinone
2 Wogonin
1 Sorafenib (brand name Nexavar)
1 5-Aminolevulinic acid
1 Auranofin
1 Astragalus
1 Allicin (mainly Garlic)
1 tamoxifen
1 Baicalin
1 Boron
1 Boswellia (frankincense)
1 Caffeic acid
1 Carnosine
1 Celastrol
1 Chlorogenic acid
1 Cinnamon
1 Bortezomib
1 diet Methionine-Restricted Diet
1 Piperine
1 Ferulic acid
1 Fenbendazole
1 flavonoids
1 Hydrogen Gas
1 Hydroxycinnamic-acid
1 itraconazole
1 Ivermectin
1 Kaempferol
1 lambertianic acid
1 Licorice
1 doxorubicin
1 Lycopene
1 Melatonin
1 Mushroom Chaga
1 Niclosamide (Niclocide)
1 Nimbolide
1 Proanthocyanidins
1 Phenethyl isothiocyanate
1 Pterostilbene
1 Rutin
1 Docetaxel
1 VitK3,menadione
1 Cisplatin
1 triptolide
1 Tumor Treating Fields
1 Arsenic trioxide
1 Selenite (Sodium)
1 Vitamin K2
1 β‐Elemene
1 γ-Tocotrienol
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:129  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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