Database Query Results : , , ATP

ATP, Adenosine triphosphate: Click to Expand ⟱
Source:
Type:
Adenosine triphosphate (ATP) is the source of energy for use and storage at the cellular level.
Cellular ATP levels are critical for cell survival, and several reports have shown that reductions in cellular ATP levels can lead to apoptosis and other types of cell death in cancer cells, depending on the level of depletion.
Adenosine triphosphate (ATP) is one of the main biochemical components of the tumor microenvironment (TME), where it can promote tumor progression or tumor suppression depending on its concentration and on the specific ecto-nucleotidases and receptors expressed by immune and cancer cells.

Cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the “Warburg effect”, and the remaining 40% is derived from mitochondrial oxidative phosphorylation.
Scientific Papers found: Click to Expand⟱
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

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↑,

5279- 3BP,  Rad,    Abstract 5243: 3-Bromopyruvate in combination with radiation inhibits pancreatic cancer growth by dismantling mitochondria and ATP generation in a preclinical mouse model
- in-vivo, PC, NA
ATP↓, ATP production was severely inhibited in cancer cells treated with same concentration of 3-BP
HK2↓, It exerts potent anticancer effects by inhibiting hexokinase II enzyme of glycolysis pathway and ATP generation in cancer cells.
RadioS↑, We also observed that 3-BP in combination with low doses of irradiation was more effective in killing cancer cells than 3-BP alone.

5278- 3BP,    The effect of 3-bromopyruvate on human colorectal cancer cells is dependent on glucose concentration but not hexokinase II expression
- in-vitro, CRC, HCT116 - in-vitro, CRC, Caco-2 - in-vitro, CRC, SW48
ATP↓, 3-Bromopyruvate (3BP) is a pyruvate analogue with alkylating properties that depletes cellular ATP levels and induces rapid cell death in neoplastic cells with limited cytotoxic effects against normal cells.
TumCD↑,
selectivity↑,
toxicity↓, 3BP treatment led to eradication of tumours of hepatocellular carcinoma cell origin in rats without apparent cytotoxic effects [19]
OS↑, first human case report suggested that 3BP was able to prolong survival in a cancer patient diagnosed with hepatocellular carcinoma in 2012 [19,20].
HK2?, 3BP is able to dissociate and inhibit mitochondrial HKII function, thereby reducing ATP production. 3BP binding also frees up binding sites previously occupied by HKII
Cyt‑c↑, llowing pro-apoptotic molecules (such as BAX and BAD) to promote the release of cytochrome c into the cytosol and induce eventual cell death
eff↑, Raji lymphoma cells grown under hypoxic conditions were more sensitive to 3BP than in normoxia
p‑Akt↑, 3BP induces rapid AKT phosphorylation at residue Thr-308

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

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

5263- 3BP,  CET,    3-Bromopyruvate overcomes cetuximab resistance in human colorectal cancer cells by inducing autophagy-dependent ferroptosis
- in-vitro, CRC, DLD1 - NA, NA, HCT116
eff↑, Our results demonstrated that the co-treatment of 3-BP and cetuximab synergistically induced an antiproliferative effect in both CRC cell lines
Ferroptosis↓, co-treatment induced ferroptosis, autophagy, and apoptosis.
TumAuto↑,
Apoptosis↑,
FOXO3↑, co-treatment inhibited FOXO3a phosphorylation and degradation and activated the FOXO3a/AMPKα/pBeclin1 and FOXO3a/PUMA pathways, leading to the promotion of ferroptosis, autophagy, and apoptosis in DLD-1
AMPKα↑,
p‑Beclin-1↑,
HK2↓, 3-Bromopyruvate (3-BP), also known as hexokinase II inhibitor II, has shown promise as an anticancer agent against various types of cancer
ATP↓, 3-BP exerts its anticancer effects by manipulating cell energy metabolism and regulating oxidative stress, as evidenced by the accumulation of reactive oxygen species (ROS) [13,14,15,16].
ROS↑,
Dose↝, Eight days postinoculation, xenografted mice were randomly divided into four groups and intraperitoneally injected with PBS, 3-BP, cetuximab, or a combination of 3-BP and cetuximab every four days for five injections.
TumVol↓, 3-BP alone or co-treatment with 3-BP and cetuximab significantly reduced the tumor volume and tumor weight on Day 28, but co-treatment showed a greater reduction than 3-BP alone
TumW↓,
xCT↑, The protein level of SLC7A11 was significantly upregulated in all three cell lines following co-treatment (Fig. 2B).
GSH↓, co-treatment with 3-BP and cetuximab led to glutathione (GSH) depletion (Fig. 2D), reactive oxygen species (ROS) production
eff↓, Knockdown of either ATG5 or Beclin1 attenuated the cell death and MDA production induced by co-treatment
MDA↑,

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].

5259- 3BP,    Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP
- in-vivo, HCC, NA
ATP↓, Advanced cancers (2-3cm) developed and were treated with the alkylating agent 3-bromopyruvate, a lactate/pyruvate analog shown here to selectively deplete ATP and induce cell death.
TumCD↑,
toxicity↓, In all 19 treated animals advanced cancers were eradicated without apparent toxicity or recurrence.
eff↑, These findings attest to the feasibility of completely destroying advanced, highly glycolytic cancers.
tumCV↓, The chemical agent 3-BrPA depletes ATP stores and inhibits HCC cell viability
Dose↝, administered eight treatments on successive days with 1 ml of 2 mM 3-BrPA, also in 1· PBS, pH 7.5. Injection of 3-BrPA was into the tumor.

5260- 3BP,    Systemic Delivery of Microencapsulated 3-Bromopyruvate for the Therapy of Pancreatic Cancer
- in-vivo, PC, NA
TumCG↓, In vivo, animals treated with β-CD–3-BrPA demonstrated minimal or no tumor progression as evident by the BLI signal
toxicity↓, In contrast to animals treated with free 3-BrPA, no lethal toxicity was observed for β-CD–3-BrPA.
BioAv↝, It is possible that in the microencapsulated formulation, 3-BrPA, is more bioavailable for uptake into tumor cells and less available to the normal cells that apparently mediate its toxicity
GAPDH↓, 3-Bromopyruvate (3-BrPA), a highly potent small-molecular inhibitor of the enzyme GAPDH, represents the only available antiglycolytic drug candidate that is able to enter cancer cells selectively through the monocarboxylate transporter 1 (MCT1; refs.
toxicity↑, However, due to its alkylating properties, 3-BrPA is associated with significant toxicity when delivered systemically in therapeutic doses, which has impeded the clinical development and use of this drug in patients with cancer
Dose↝, Encapsulation of 3-BrPA in β-CD was achieved by portionwise addition of 3-BrPA (166 mg, 1 mmol/L) to a stirring solution of β-CD (1,836 mg in 30 mL DI water). The resulting solution was sonicated for 1 hour at room temperature and then shaken overnig
ATP↓, ability of microencapsulated 3-BrPA (β-CD-3-BrPA) to achieve dose-dependent ATP depletion and cell death, two human pancreatic cancer cell lines were employed.
eff↑, both PDAC cell lines were more sensitive to the drugs when hypoxic (Fig. 2)
TumCI↓, MiaPaCa-2 and Suit-2 cells showed a reduction in invasion at drug concentrations as low as 12.5 µmol/L.
MMP9↓, marked reduction in the secretion of MMP-9 was detected in both cell lines.
toxicity↓, No organ toxicities or tissue damage was observed in animals treated with β-CD–3-BrPA

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↓,

3864- ACNs,    Anthocyanins Potentially Contribute to Defense against Alzheimer’s Disease
- Review, AD, NA
*antiOx↑, ANTs are potent antioxidants that might regulate the free radical-mediated generation of amyloid peptides (Abeta-amyloids) in the brain
*Aβ↓,
*ROS↓,
*cognitive↑, Mulberries are a rich source of ANTs that induce antioxidant enzymes and promote cognition
*APP↓, In the cerebral cortex, blackcurrant and bilberry extract reduced APP levels in AD mouse models, but changes in the expression or phosphorylation of tau-protein were not observed
*BBB↑, ANTs cross the blood-brain barrier and protect brain tissue from Abeta toxicity
*Ca+2↓, Aronia melanocarpa. ANTs of this plant decrease intracellular calcium and ROS but increase ATP and mitochondrial potential.
*ATP↑,
*BACE↓, An-NPs also attenuate the protein expression of BACE-1 neuroinflammatory markers, such as phosphonuclear factor kB (p-NF-kB), tumor-necrosis factor (TNF-α), and inducible nitric oxide synthase (iNOS),
*p‑NF-kB↓,
*TNF-α↓,
*iNOS↓,

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

373- AgNPs,    Cytotoxic Potential and Molecular Pathway Analysis of Silver Nanoparticles in Human Colon Cancer Cells HCT116
- in-vitro, Colon, HCT116
LDH↓, Increased lactate dehydrogenase leakage (LDH),
ROS↑,
MDA↑,
ATP↓,
GSH↓,
MMP↓, loss of

4383- AgNPs,    Exploring the Potentials of Silver Nanoparticles in Overcoming Cisplatin Resistance in Lung Adenocarcinoma: Insights from Proteomic and Xenograft Mice Studies
- in-vitro, Lung, A549 - in-vivo, Lung, A549
Apoptosis↑, Silver nanoparticles (AgNPs) have shown great potential as therapeutic agents due to their ability to cause apoptotic cell death in cancer cells.
VEGF↓, suppressing the VEGF signaling pathway, repressing p53-mediated pathways, promoting cell cycle arrest,
P53↓,
TumCCA↑,
ROS↑, we found that AgNPs induced ROS generation
AntiTum↑, AgNPs exhibit similar antitumoral effects on both A549 and A549/DDP-bearing mice.
eff↑, AgNPs are internalized by cells far more effectively than free Ag+ under identical exposure conditions
ATP↓, AgNPs exposure also decreased basal respiration (52.3 ± 4.6 pmol/min/106 cells), maximal respiration (109.2 ± 12.2 pmol/min/106 cells), ATP production (
eff↑, These results explain why AgNPs remain effective against cisplatin-resistant A549 cells.
CTR1↑, recent studies have shown that AgNPs treatment significantly upregulates CTR1

4549- AgNPs,    Silver nanoparticles: Synthesis, medical applications and biosafety
- Review, Var, NA - Review, Diabetic, NA
ROS↑, action mechanisms of AgNPs, which mainly involve the release of silver ions (Ag+), generation of reactive oxygen species (ROS), destruction of membrane structure.
eff↑, briefly introduce a new type of Ag particles smaller than AgNPs, silver Ångstrom (Å, 1 Å = 0.1 nm) particles (AgÅPs), which exhibit better biological activity and lower toxicity compared with AgNPs.
other↝, This method involves reducing silver ions to silver atoms 9, and the process can be divided into two steps, nucleation and growth
DNAdam↑, antimicrobial mechanisms of AgNPs includes destructing bacterial cell walls, producing reactive oxygen species (ROS) and damaging DNA structure
EPR↑, Due to the enhanced permeability and retention (EPR) effect, tumor cells preferentially absorb NPs-sized bodies than normal tissues
eff↑, Large surface area may lead to increased silver ions (Ag+) released from AgNPs, which may enhance the toxicity of nanoparticles.
eff↑, Our team prepared Ångstrom silver particles, capped with fructose as stabilizer, can be stable for a long time
TumMeta↓, AgNPs can induce tumor cell apoptosis through inactivating proteins and regulating signaling pathways, or blocking tumor cell metastasis by inhibiting angiogenesis
angioG↓, Various studies support that AgNPs can deprive cancer cells of both nutrients and oxygen via inhibiting angiogenesis
*Bacteria↓, Rather than Gram-positive bacteria, AgNPs show a stronger effect on the Gram-negative ones. This may be due to the different thickness of cell wall between two kinds of bacteria
*eff↑, In general, as particle size decreases, the antibacterial effect of AgNPs increases significantly
*AntiViral↑, AgNPs with less than 10 nm size exhibit good antiviral activity 185, 186, which may be due to their large reaction area and strong adhesion to the virus surface.
*AntiFungal↑, Some studies confirm that AgNPs exhibit good antifungal properties against Colletotrichum coccodes, Monilinia sp. 178, Candida spp.
eff↑, The greater cytotoxicity and more ROS production are observed in tumor cells exposed to high positive charged AgNPs
eff↑, Nanoparticles exposed to a protein-containing medium are covered with a layer of mixed protein called protein corona. formation of protein coronas around AgNPs can be a prerequisite for their cytotoxicity
TumCP↓, Numerous experiments in vitro and in vivo have proved that AgNPs can decrease the proliferation and viability of cancer cells.
tumCV↓,
P53↝, gNPs can promote apoptosis by up- or down-regulating expression of key genes, such as p53 242, and regulating essential signaling pathways, such as hypoxia-inducible factor (HIF) pathway
HIF-1↓, Yang et al. found that AgNPs could disrupt the HIF signaling pathway by attenuating HIF-1 protein accumulation and downstream target genes expression
TumCCA↑, Cancer cells treated with AgNPs may also show cell cycle arrest 160, 244
lipid-P↑, Ag+ released by AgNPs induces oxidation of glutathione, and increases lipid peroxidation in cellular membranes, resulting in cytoplasmic constituents leaking from damaged cells
ATP↓, mitochondrial function can be inhibited by AgNPs via disrupting mitochondrial respiratory chain, suppressing ATP production
Cyt‑c↑, and the release of Cyt c, destroy the electron transport chain, and impair mitochondrial function
MMPs↓, AgNPs can also inhibit the progression of tumors by inhibiting MMPs activity.
PI3K↓, Various studies support that AgNPs can deprive cancer cells of both nutrients and oxygen via inhibiting angiogenesis
Akt↓,
*Wound Healing↑, AgNPs exhibit good properties in promoting wound repair and bone healing, as well as inhibition of inflammation.
*Inflam↓,
*Bone Healing↑,
*glucose↓, blood glucose level of diabetic rats decreased when treated with AgNPs for 14 days and 21 days without significant acute toxicity.
*AntiDiabetic↑,
*BBB↑, The small-sized AgNPs are easy to penetrate the body and cross biological barriers like the blood-brain barrier and the blood-testis barrier

4542- AgNPs,    Silver Nanoparticles (AgNPs): Comprehensive Insights into Bio/Synthesis, Key Influencing Factors, Multifaceted Applications, and Toxicity─A 2024 Update
- Review, NA, NA
AntiCan↑, cytotoxicity against human colon carcinoma (HT-29) cells. The MTT assay confirmed their anticancer potential, with an IC50 value of 150.8 μg/mL.
DNAdam↑, Ag-NPs, accumulating in the nucleus, may cause genotoxicity, DNA damage, and chromosomal aberrations
ATP↓, Ag-NP exposure disrupts calcium homeostasis, leading to mitochondrial dysfunction, ATP depletion, and apoptosis.
Apoptosis↑,
ROS↓, induce cytotoxicity through numerous mechanisms viz., oxidative stress, mitochondrial dysfunction, DNA damage, cell cycle arrest, and subsequent apoptosis.
TumCCA↑,
*Bacteria↓, effectiveness as an antibacterial agent.
*BMD↑, Bone Repair Applications

2287- AgNPs,    Silver nanoparticles induce endothelial cytotoxicity through ROS-mediated mitochondria-lysosome damage and autophagy perturbation: The protective role of N-acetylcysteine
- in-vitro, Nor, HUVECs
*TumCP↓, AgNPs affects the morphology and function of endothelial cells which manifests as decreased cell proliferation, migration, and angiogenesis ability
*ROS↑, AgNPs can induce excessive cellular production of reactive oxygen species (ROS), leading to damage to cellular sub-organs such as mitochondria and lysosomes
*eff↓, treatment with ROS scavenger-NAC can effectively suppress AgNP-induced endothelial damage.
*MDA↑, exposure to AgNPs increased MDA levels and decreased GSH levels.
*GSH↓,
*MMP↓, significantly reduced both MMP and ATP levels (Fig. 7) in HUVECs,
*ATP↓,
*LC3II↑, expression levels of LC3-II and p62 were significantly increase
*p62↑,
*Bcl-2↓, the anti-apoptotic protein expression level of Bcl-2 in HUVECs decreased, while the pro-apoptotic protein expression levels of Bax and Caspase-3 increased significantly.
*BAX↑,
*Casp3↑,

2656- AL,    Allicin Protects PC12 Cells Against 6-OHDA-Induced Oxidative Stress and Mitochondrial Dysfunction via Regulating Mitochondrial Dynamics
- in-vitro, Park, PC12
*antiOx↑, Allicin, the main biologically active compound derived from garlic, has been shown to exert various anti-oxidative and anti-apoptotic activities in in vitro and in vivo studies.
*Apoptosis↓, allicin treatment significant increased cell viability, and decreased LDH release and apoptotic cell death after 6-OHDA exposure
*LDH↓,
ROS↓, Allicin also inhibited ROS generation
*lipid-P↓, reduced lipid peroxidation and preserved the endogenous antioxidant enzyme activities.
*mtDam↓, These protective effects were associated with suppressed mitochondrial dysfunction,
*MMP↓, as evidenced by decreased MMP collapse and cytochrome c release,
*Cyt‑c↓,
*ATP∅, preserved mitochondrial ATP synthesis,
*Ca+2↝, and the promotion of mitochondrial Ca(2+) buffering capacity
*neuroP↑, allicin treatment can exert protective effects against PD related neuronal injury through inhibiting oxidative stress and mitochondrial dysfunction with dynamic changes.

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↑,

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↓,

3447- ALA,    Redox Active α-Lipoic Acid Differentially Improves Mitochondrial Dysfunction in a Cellular Model of Alzheimer and Its Control Cells
- in-vitro, AD, SH-SY5Y
*ATP↑, Incubation with ALA showed a significant increase in ATP levels in both SH-SY5Y-APP695 and SH-SY5Y-MOCK cells.
*MMP↑, MMP levels were elevated in SH-SY5Y-MOCK cells, treatment with rotenone showed a reduction in MMP, which could be partly alleviated after incubation with ALA in SH-SY5Y-MOCK cells.
*ROS↓, ROS levels were significantly lower in both cell lines treated with ALA.
*GlucoseCon↑, benefits to diabetic neuropathy and impaired glucose uptake, and the regeneration of glutathione (GSH) and vitamins C and E
*GSH↑,
*neuroP↑, ALA seems to have a positive effect on neurodegenerative diseases such as AD
*cognitive↑, ALA improves cognitive performance and could be considered as a promising bioactive substance for AD by affecting multiple mechanisms such as:
*Ach↑, (1) impaired acetylcholine production;
*Inflam↓, (2) hydroxyl radical formation, ROS production, and neuroinflammation;
*Aβ↓, (3) impaired amyloid plaque formation;
OXPHOS↓, ALA has also been shown to restore the expression of OXPHOS complexes in HepG2 cells, ranging in a concentration between 0.5–2 mM

3545- ALA,    Potential therapeutic effects of alpha lipoic acid in memory disorders
- Review, AD, NA
*neuroP↑, potential therapeutic effects for the prevention or treatment of neurodegenerative disease
*Inflam↓, ALA is able to regulate inflammatory cell infiltration into the central nervous system and to down-regulate VCAM-1 and human monocyte adhesion to epithelial cells
*VCAM-1↓, down-regulate vascular cell adhesion molecule-1 (VCAM-1) and the human monocyte adhesion to epithelial cells
*5HT↑, ALA is able to improve the function of the dopamine, serotonin and norepinephrine neurotransmitters
*memory↑, scientific evidence shows that ALA possesses the ability to improve memory capacity in a number of experimental neurodegenerative disease models and in age-related cognitive decline in rodents
*BioAv↝, Between 27 and 34% of the oral intake is available for tissue absorption; the liver is one of the main clearance organs on account of its high absorption and storage capacity
*Half-Life↓, The plasma half-life of ALA is approximately 30 minutes. Peak urinary excretion occurs 3-6 hours after intake.
*NF-kB↓, As an inhibitor of NF-κβ, ALA has been studied in cytokine-mediated inflammation
*antiOx↑, In addition to the direct antioxidant properties of ALA, some studies have shown that both ALA and DHLA and a great capacity to chelate redox-active metals, such as copper, free iron, zinc and magnesium, albeit in different ways (
*IronCh↑, ALA is able to chelate transition metal ions and, therefore, modulate the iron- and copper-mediated oxidative stress in Alzheimer’s plaques
*ROS↓, iron and copper chelation with DHLA may explain the low level of free radical damage in the brain and the improvement in the pathobiology of Alzheimer’s Disease
*ATP↑, ALA may increase the mitochondrial synthesis of ATP in the brain of elderly rats, thereby increasing the activity of the mitochondrial enzymes
*ChAT↑, ALA may also play a role in the activation of the choline acetyltransferase enzyme (ChAT), which is essential in the anabolism of acetylcholine
*Ach↑,
*cognitive↑, One experimental study has shown that in rats that had been administered ALA there was an inversion in the cognitive dysfunction with an increase in ChAT activity in the hippocampus
*lipid-P↓, administration of ALA reduces lipid peroxidation in different areas of the brain and increases the activity of antioxidants such as ascorbate (vitamin C), α-tocopherol (vitamin E), glutathione,
*VitC↑,
*VitE↑,
*GSH↑,
*SOD↑, and also the activity of superoxide dismutase, catalase, glutathione-peroxidase, glutathione-reductase, glucose-6-P-dehydrogenase
*Catalase↑,
*GPx↑,
*Aβ↓, Both ALA and DHLA have been seen to inhibit the formation of Aβ fibrils

5326- ALC,    L-Carnitine Is an Endogenous HDAC Inhibitor Selectively Inhibiting Cancer Cell Growth In Vivo and In Vitro
- vitro+vivo, Liver, HepG2
TumCG↓, Here we found that (1) LC treatment selectively inhibited cancer cell growth in vivo and in vitro;
P21↑, (2) LC treatment selectively induces the expression of p21cip1 gene, mRNA and protein in cancer cells
ac‑H3↑, (4) LC increases histone acetylation and induces accumulation of acetylated histones both in normal thymocytes and cancer cells
HDAC↓, (5) LC directly inhibits HDAC I/II activities via binding to the active sites of HDAC and induces histone acetylation and lysine-acetylation accumulation in vitro;
*ATP↑, LC is able to generate ATP in normal mouse thymocytes, but not in hepatic HepG2 and SMMC-7721 cancer cells.
selectivity↑,
ac‑H4↑, LC dose-dependently increased acetylation of H3 and H4 (

1349- And,    Andrographolide promoted ferroptosis to repress the development of non-small cell lung cancer through activation of the mitochondrial dysfunction
- in-vitro, Lung, H460 - in-vitro, Lung, H1650
TumCG↓,
TumMeta↓,
Ferroptosis↑,
ROS↑,
MDA↑,
Iron↑,
GSH↓, lipid ROS reduced glutathione (GSH) accumulation
GPx4↓,
xCT↓, SLC7A11
MMP↓,
ATP↓,

1536- Api,    Apigenin causes necroptosis by inducing ROS accumulation, mitochondrial dysfunction, and ATP depletion in malignant mesothelioma cells
- in-vitro, MM, MSTO-211H - in-vitro, MM, H2452
tumCV↓,
ROS↑, increase in intracellular reactive oxygen species (ROS)
MMP↓, caused the loss of mitochondrial membrane potential (ΔΨm)
ATP↓, ATP depletion
Apoptosis↑,
Necroptosis↑,
DNAdam↑,
TumCCA↑, delay at the G2/M phase of cell cycle
Casp3↑,
cl‑PARP↑,
MLKL↑,
p‑RIP3↑,
Bax:Bcl2↑,
eff↓, ATP supplementation restored cell viability and levels of DNA damage-, apoptosis- and necroptosis-related proteins that apigenin caused.
eff↓, N-acetylcysteine reduced ROS production and improved ΔΨm loss and cell death that were caused by apigenin.

591- Api,  doxoR,    Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines
- in-vitro, AML, Jurkat - in-vitro, AML, THP1
ATP↓,
Casp3↑,
γH2AX↑,

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

566- ART/DHA,  2DG,    Dihydroartemisinin inhibits glucose uptake and cooperates with glycolysis inhibitor to induce apoptosis in non-small cell lung carcinoma cells
- in-vitro, Lung, A549 - in-vitro, Lung, PC9
GlucoseCon↓,
ATP↓,
lactateProd↓,
p‑S6↓,
mTOR↓,
GLUT1↓,
Casp9↑,
Casp8↑,
Casp3↑,
Cyt‑c↑,
AIF↑,
ROS↑, generation of ROS is critical for the toxic effects of DHA

1355- Ash,    Withaferin A-Induced Apoptosis in Human Breast Cancer Cells Is Mediated by Reactive Oxygen Species
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vitro, Nor, HMEC
eff↑, WA treatment caused ROS production in MDA-MB-231 and MCF-7 cells, but not in a normal human mammary epithelial cell line (HMEC). ****
mt-ROS↑, WA-induced apoptosis in human breast cancer cells is mediated by mitochondria-derived ROS
mitResp↓,
OXPHOS↓, WA exposure was accompanied by inhibition of oxidative phosphorylation and inhibition of complex III activity.
compIII↑,
BAX↑,
Bak↑,
other↓, Cu,Zn-Superoxide dismutase (Cu,Zn-SOD) overexpression confers protection against WA-induced ROS production and apoptosis
ATP∅, steady-state levels of ATP were unaffected by WA treatment in either cell line
*ROS∅, but not in a normal human mammary epithelial cell line (HMEC). WA treatment caused ROS production in breast cancer cells, HMEC were resistant to pro-oxidant effect of this agent.

5173- Ash,  2DG,    Withaferin A inhibits lysosomal activity to block autophagic flux and induces apoptosis via energetic impairment in breast cancer cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468 - in-vitro, BC, T47D
autoF↓, WFA blocks autophagy flux and lysosomal proteolytic activity in breast cancer cells.
lysosome↓, WFA treatment inhibits lysosomal activity
TumAuto↑, WFA increases accumulation of autophagosomes, LC3B-II conversion, expression of autophagy-related proteins and autophagosome/lysosome fusion.
p‑LDH↓, WFA decreases expression and phosphorylation of lactate dehydrogenase, the key enzyme that catalyzes pyruvate-to-lactate conversion
ATP↓, reduces adenosine triphosphate levels and increases AMP-activated protein kinase (AMPK) activation.
AMPK↑,
eff↑, WFA and 2-deoxy-d-glucose combination elicits synergistic inhibition of breast cancer cells.
TumCG↓, WFA inhibits breast cancer growth and increases intracellular autophagosomes and autophagy markers
CTSD↓, we found that WFA impaired the maturation of Cathepsin D (CTSD)
CTSB↓, Inhibition of CTSD maturation also indicated reduced CTSB and CTSL activity as they are essential for the cleavage of CTSD.
CTSL↑,
cl‑PARP1↑, WFA and 2-DG treatment also showed higher cleavage of PARP1 in breast cancer cells
LDHA↓, WFA treatment effectively reduces the expression of LDHA in breast cancer cells
TCA↓, d leads to insufficient substrates for TCA cycle,

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↓,

3159- Ash,    Neuroprotective effects of Withania somnifera in the SH-SY5Y Parkinson cell model
- in-vitro, Park, SH-SY5Y
*neuroP↑, Neuroprotective effects of Withania somnifera
*Inflam↓, including inflammation and oxidative stress reduction, memory and cognitive function improvement.
*ROS↓,
*cognitive↑,
*memory↑,
*GPx↑, significantly increased glutathione peroxidase activity
*Prx↓, KSM-66, had peroxiredoxin-1 and VGF levels significantly lower than the untreated control
*ATP↑, rescue of mitochondria with 0.5 mg/ml KSM-66 extract showed an increase in ATP levels.
*Vim↓, Pre-treatment with KSM-66 decreased level of vimentin
*mtDam↓, KSM-66 attenuates 6-OHDA-induced mitochondrial dysfunction in SH-SY5Y cells

5362- AV,    Anti-cancer effects of aloe-emodin: a systematic review
- Review, Var, NA
AntiCan↑, Aloe-emodin possesses multiple anti-proliferative and anti-carcinogenic properties in a host of human cancer cell lines, with often multiple vital pathways affected by the same molecule.
eff↝, The effects of aloe-emodin are not ubiquitous across all cell lines but depend on cell type.
TumCP↓, most notable effects include inhibition of cell proliferation, migration, and invasion; cycle arrest; induction of cell death;
TumCMig↓,
TumCI↓,
TumCCA↑,
TumCD↑,
MMP↓, mitochondrial membrane and redox perturbations; and modulation of immune signaling.
ROS↑, which coincide with deleterious effects on mitochondrial membrane permea-bility and/or oxidative stress via exacerbated ROS production.
Apoptosis↑, In bladder cancer cells (T24), aloe-emodin induced time-and dose-dependent apoptosis [7]
CDK1↓, reduced levels of cyclin-dependent kinase (CDK) 1, cyclin B1, and BCL-2 after treatment with aloe-emodin.
CycB/CCNB1↓,
Bcl-2↓,
PCNA↓, Increases in cyclin B1, CDK1, and alkaline phosphatase (ALP) activity were observed along with inhibition of proliferating cell nuclear antigen (PCNA), showing decreased proliferation.
ATP↓, human lung non-small cell car¬cinoma (H460). They found a time- de¬pendent reduction in ATP, lower ATP synthase expression
ER Stress↑, hypothesized to cause apoptosis by augmenting endoplasmic reticulum stress [16].
cl‑Casp3↑, (HepG2) cells underwent apoptosis through a cas-pase-dependent pathway with cleavage and activation of caspases-3/9 and cleavage of PARP [24]
cl‑Casp9↑,
cl‑PARP↑,
MMP2↓, Matrix metalloproteinase-2 was significantly decreased, with an increase in ROS and cytosolic calcium.
Ca+2↑,
DNAdam↑, U87 malignant glioma cells through disruption of mitochondrial membrane potential, cell cycle arrest in the S phase, and DNA fragmentation in a time-dependent manner with minimal necrosis
Akt↓, Prostate cancer. Following treatment with aloe-emodin, mTORC2's down¬stream enzymes, AKT and PKCa, were inhibited
PKCδ↓,
mTORC2↓, Proliferation of PC3 cells was inhibited as a result of aloe-emodin binding to mTORC2, with inhibition of mTORC2 kinase activity.
GSH↓, Skin cancer. Intracellular ROS increased, while intra-cellular-reduced glutathione (GSH) was depleted and BCL-2 (anti-apoptotic protein) was down-regulated.
ChemoSen↑, Aloe-emodin also sensitizes skin cancer cells to chemo-therapy. aloe-emodin and emodin potentiated the therapeutic effects of cisplatin, doxo-rubicin, 5-fluorouracil

1395- BBR,    Analysis of the mechanism of berberine against stomach carcinoma based on network pharmacology and experimental validation
- in-vitro, GC, NA
Apoptosis↑,
ROS↑,
MMP↓,
ATP↓,
AMPK↑,
TP53↑,
p‑MAPK↓, decreased phosphorylated-MAPK3/1 expression
p‑ERK↓,

1379- BBR,    Berberine derivative DCZ0358 induce oxidative damage by ROS-mediated JNK signaling in DLBCL cells
- in-vitro, lymphoma, NA
TumCP↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
TumCCA↑, G0/G1 phase
MMP↓,
Ca+2↑,
ATP↓, decreased intracellular adenosine triphosphate production,
mtDam↑, mitochondrial dysfunction
Apoptosis↑,
ROS↑,
JNK↑,
eff↓, treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358.

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

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.

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↑,

2735- BetA,    Betulinic acid as apoptosis activator: Molecular mechanisms, mathematical modeling and chemical modifications
- Review, Var, NA
mt-Apoptosis↑, BA and analogues (BAs) have been known to exhibit potential antitumor action via provoking the mitochondrial pathway of apoptosis
Casp↑, cytosolic caspase activation
p38↑, inhibition of pro-apoptotic p38, MAPK and SAP/JNK kinases [8],
MAPK↓,
JNK↓,
VEGF↓, decreased expression of pro-apoptotic proteins and vascular endothelial growth factor (VEGF)
AIF↑, BA was recognized to trigger the process of apoptosis in human metastatic melanoma cells (Me-45) by releasing apoptosis inducing factor (AIF) and cytochrome c (Cyt C) through mitochondrial membrane
Cyt‑c↑,
ROS↑, BA also stimulates the increased production of reactive oxygen species (ROS) that is considered a stress factor involved in initiating mitochondrial membrane permeabilization
Ca+2↑, Moreover, the calcium overload and thereby ATP depletion are other stress factors causing enhanced inner mitochondrial membrane permeability via nonspecific pores formation
ATP↓,
NF-kB↓, BA has also known to be involved in activation of nuclear factor kappa B (NF-κB) that is responsible for apoptosis induction in variety of cancer cells
ATF3↓, According to Zhang et al. [14], BA stimulates apoptosis through the suppression of cyclic AMP-dependent transcription factor ATF-3 and NF-κB pathways and downregulation of p53 gene.
TOP1↓, inhibition of topoisomerases
VEGF↓, ecreased expression of vascular endothelial growth (VEGF) and the anti-apoptotic protein surviving in LNCaP prostate cancer cells.
survivin↓,
Sp1/3/4↓, selective proteasome-dependent targeted degradation of transcription factors specificity proteins (Sp1, Sp3, and Sp4), which generally regulate VEGF and survivin expression and highly over-expressed in tumor conditions
MMP↓, perturbed mitochondrial membrane potential
ChemoSen↑, BA can support as sensitizer in combination therapy to enhance the anticancer effects with minimum side effects.
selectivity↑, Normal human fibroblasts [41], peripheral blood lymphoblasts [41], melanocytes [32] and astrocytes [30] were found to be resistant to BA in vitro
BioAv↓, The clinical use of BA is seriously challenging due to high hydrophobicity which subsequently causes poor bioavailability
BioAv↑, A BA-loaded oil-in-water nanoemulsion was developed using phospholipase-catalyzed modified phosphatidylcholine as emulsifier in an ultrasonicator [120].
BioAv↑, Aqueous solubility of BA may also be increased through grinding with hydrophilic polymers (polyethylene glycol, polyvinylpyrrolidone, arabinogalactan) [121,122].
BioAv↑, Subsequently, for further improvement in biocompatibility, a technique of nanotube coating was employed with four biopolymers i.e. polyethylene glycol (PEG), chitosan, tween 20 and tween 80.
BioAv↑, Similarly, BA-coated silver nanoparticles displayed an improved antiproliferative and antimigratory activity, particularly against melanoma cells (A375: murine melanoma cells)

696- Bor,    Nothing Boring About Boron
- Review, Var, NA
*hs-CRP↓, reduces levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor μ (TNF-μ);
*TNF-α↓,
*SOD↑, raises levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase
*Catalase↑,
*GPx↑,
*cognitive↑, improves the brains electrical activity, cognitive performance, and short-term memory for elders; restricted boron intake adversely affected brain function and cognitive performance.
*memory↑, In humans, boron deprivation (<0.3 mg/d) resulted in poorer performance on tasks of motor speed and dexterity, attention, and short-term memory.
*Risk↓, Boron-rich diets and regions where the soil and water are rich in boron correlate with lower risks of several types of cancer, including prostate, breast, cervical, and lung cancers.
*SAM-e↑,
*NAD↝, Boron strongly binds oxidized NAD+,76 and, thus, might influence reactions in which NAD+ is involved
*ATP↝,
*Ca+2↝, Because of its positive charge, magnesium stabilizes cell membranes, balances the actions of calcium, and functions as a signal transducer
HDAC↓, some boronated compounds are histone deacetylase inhibitors
TumVol↓,
IGF-1↓, expression of IGF-1 in the tumors was significantly reduced by boron treatment
PSA↓, Boronic acid has been shown to inhibit PSA activity.
Cyc↓, boric acid inhibits the growth of prostate-cancer cells both by decreasing expression of A-E cyclin
TumCMig↓,
*serineP↓, Boron exists in the human body mostly in the form of boric acid, a serine protease inhibitor.
HIF-1↓, shown to greatly inhibit hypoxia-inducible factor (HIF) 1
*ChemoSideEff↓, An in vitro study found that boric acid can help protect against genotoxicity and cytotoxicity that are induced in lymphocytes by paclitaxel
*VitD↑, greater production of 25-hydroxylase, and, thus, greater potential for vitamin-D activation
*Mag↑, Boron significantly improves magnesium absorption and deposition in bone
*eff↑, boron increases the biological half-life and bioavailability of E2 and vitamin D.
Risk↓, risk of prostate cancer was 52% lower in men whose diets supplied more than 1.8 mg/d of boron compared with those whose dietary boron intake was less than or equal to 0.9 mg/d.
*Inflam↓, As research into the chemistry of boron-containing compounds has increased, they have been shown to be potent antiosteoporotic, anti-inflammatory, and antineoplastic agents
*neuroP↑, In addition, boron has anti-inflammatory effects that can help alleviate arthritis and improve brain function and has demonstrated such significant anticancer
*Calcium↑, increase serum levels of estradiol and calcium absorption in peri- and postmenopausal women.
*BMD↑, boron stimulates bone growth in vitamin-D deficient animals and alleviates dysfunctions in mineral metabolism characteristic of vitamin-D deficiency
*chemoP↑, may help ameliorate the adverse effects of traditional chemotherapeutic agents. boric acid can help protect against genotoxicity and cytotoxicity that are induced in lymphocytes by paclitaxel, an anticancer drug commonly used to treat breast, ovarian
AntiCan↑, demonstrated preventive and therapeutic effects in a number of cancers, such as prostate, cervical, and lung cancers, and multiple and non-Hodgkin’s lymphoma
*Dose↑, only an upper intake level (UL) of 20 mg/d for individuals aged ≥ 18 y.
*Dose↝, substantial number of articles showing benefits support the consideration of boron supplementation of 3 mg/d for any individual who is consuming a diet lacking in fruits and vegetables
*BMPs↑, Boron was also found to increase mRNA expression of alkaline phosphatase and bone morphogenetic proteins (BMPs)
*testos↑, 1 week of boron supplementation of 6 mg/d, a further study by Naghii et al20 of healthy males (n = 8) found (1) a significant increase in free testosterone,
angioG↓, Inhibition of tumor-induced angiogenesis prevents growth of many types of solid tumors and provides a novel approach for cancer treatment; thus, HIF-1 is a target of antineoplastic therapy.
Apoptosis↑, Cancer cells, however, commonly overexpress sugar transporters and/or underexpress borate export, rendering sugar-borate esters as promising chemopreventive agents
*selectivity↑, In normal cells, the 2 latter, cell-destructive effects do not occur because the amount of borate present in a healthy diet, 1 to 10 mg/d, is easily exported from normal cells.
*chemoPv↑, promising chemopreventive agents

2778- Bos,    Development, Analytical Characterization, and Bioactivity Evaluation of Boswellia serrata Extract-Layered Double Hydroxide Hybrid Composites
- in-vitro, Nor, NA
*ATP↓, this extract is largely composed of terpene substances that are known to be able to bind to the membrane, thus causing the formation of irreversible pores, and they can lower protein synthesis, reducing ATP consumption
*ROS↓, well-known scavenger ability of the boswellic acids [49,50] was expected to significantly reduce the amount of the cytotoxic oxygen- and nitrogen-derived (ROS)

2348- CAP,    Recent advances in analysis of capsaicin and its effects on metabolic pathways by mass spectrometry
- Analysis, Nor, NA
Warburg↓, Capsaicin inhibits the Warburg effect by binding directly to Cys424 residue and LDHA of pyruvate kinase isoenzyme type M2 (PKM2).
*PKM2↓,
*COX2↓, capsaicin targets COX-2 and down-regulates its expression, which results in the further inhibition of inflammation
*Inflam↓,
*Sepsis↓, capsaicin may be used as a new active ingredient to treat sepsis and inflammation
*AMPK↑, capsaicin activates adenylate-activated protein kinase (AMPK) and protein kinase A (PKA), in turn enhancing the activity of the mitochondrial respiratory chain and promoting fatty acid oxidation
*PKA↑,
*mitResp↑,
*FAO↑,
*FASN↓, capsaicin can inhibit the activity of fatty acid synthetase
*PGM1?,
*ATP↑, treatment resulted in increased intracellular ATP levels (the end product of glycolysis)
*ROS↓, Capsaicin can mitigate the negative effects of oxidative stress on human health by scavenging these free radicals and reducing the oxidative stress response.

1259- CAP,    Capsaicin inhibits HIF-1α accumulation through suppression of mitochondrial respiration in lung cancer cells
- in-vitro, Lung, H1299 - in-vitro, Lung, A549 - in-vitro, Lung, H23 - in-vitro, Lung, H2009
Hif1a↓, Under hypoxic conditions, capsaicin reduced the accumulation of HIF-1α protein
PDK1↓,
GLUT1↓,
ROS↑,
mitResp↓,
ATP↓,

2014- CAP,    Role of Mitochondrial Electron Transport Chain Complexes in Capsaicin Mediated Oxidative Stress Leading to Apoptosis in Pancreatic Cancer Cells
- in-vitro, PC, Bxpc-3 - in-vitro, Nor, HPDE-6 - in-vivo, PC, AsPC-1
ROS↑, ROS was about 4–6 fold more as compared to control and as early as 1 h after capsaicin treatment in BxPC-3 and AsPC-1 cells
*ROS∅, but not in normal HPDE-6 cells
selectivity↑, only small ~1.2fold ROS increase in normal cell
compI↓, capsaicin inhibits about 2.5–9% and 5–20% of complex-I activity
compIII↓, and 8–75% of complex-III activity in BxPC-3 and AsPC-1 cells respectively
eff↑, which was attenuable by SOD, catalase and EUK-134.
selectivity↑, capsaicin treatment failed to inhibit complex-I or complex-III activities in normal HPDE-6 cells
ATP↓, ATP levels were drastically suppressed by capsaicin treatment in both BxPC-3 and AsPC-1 cells
Cyt‑c↑, release of cytochrome c and cleavage of both caspase-9 and caspase-3 due to disruption of mitochondrial membrane potential
Casp9↑,
Casp3↑,
MMP↓,
SOD↓, mice orally fed with 2.5 mg/kg capsaicin show decreased SOD activity and an increase in GSSG/GSH levels as compared to controls
GSH/GSSG↓, mice orally fed with 2.5 mg/kg capsaicin
Apoptosis↑, Capsaicin triggers apoptosis in pancreatic cancer cells but not in normal HPDE-6 cells
*toxicity∅, Capsaicin triggers apoptosis in pancreatic cancer cells but not in normal HPDE-6 cells
GSH↓, Taken together, our results suggest that depletion of GSH level and inhibition of SOD, catalase and GPx by capsaicin disturbs the cellular redox homeostasis resulting in increased oxidative stress.
Catalase↓,
GPx↓,
Dose↝, 13.2 mg dose of capsaicin for a 60 kg person

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

2315- Citrate,    Why and how citrate may sensitize malignant tumors to immunotherapy
- Review, Var, NA
Bcl-2↓, SCT can induce silent apoptosis by reducing expression of key pro-apoptotic proteins (Bcl-2, surviving, MCL1), and promoting the activation of caspases-3 and −9 and −8, as showed in multiple cancer cell lines
Mcl-1↓,
survivin↓,
Casp3↑,
Casp9↑,
Ferroptosis↑, SCT can also trigger ferroptosis, an iron-dependent form of lytic cell death inducing lipid peroxidation (LPO)
lipid-P↑,
Ca+2↓, citrate lowers mitochondrial Ca2+ concentration by chelation
Akt↓, by chelating cytosolic Ca2+, citrate inhibits the Ca2+/CAMKK2/AKT/mTOR signaling pathway, thereby suppressing HIF1-α dependent glycolysis
mTOR↓,
Hif1a↓,
MCU↓, reduces the activity of the mitochondrial calcium uniporter (MCU), resulting in decreasing ATP production, increasing ROS production
ATP↓,
ROS↑,
eff↑, Of note, ferroptosis can enhance the effectiveness of immunotherapy, as showed in glioma models

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.

1583- Citrate,    Extracellular citrate and metabolic adaptations of cancer cells
- Review, NA, NA
Warburg↓, hypothesis that extracellular citrate might play a major role in cancer metabolism and is responsible for a switch between Warburg effect and OXPHOS
OXPHOS↓,
Dose∅, 10 mM citrate, cancer cells were shown to have decreased proliferation, ATP synthesis,
TumCP↓,
ATP↓,
eff↑, increased apoptosis and sensitivity to cis-platin
Apoptosis↑,
TumCG↓, high doses of citrate in vivo decreased tumour growth
PFK1↓, increased levels of cytosolic citrate taken up from the extracellular space would decrease phosphofructokinase-1 (PFK-1) activity

1587- Citrate,    ATP citrate lyase: A central metabolic enzyme in cancer
- Review, NA, NA
ACLY↓, administration of citrate at high level mimics a strong inhibition of ACLY and could be tested to strengthen the effects of current therapies. -a strong ACLY inhibition could be mimicked by by flooding the cytosol with citrate.
other↓, ACLY inhibition by simple drugs such as HCA or bempedoic acid should be tested, optimally associated with glycolytic inhibitors (or glucose starvation diet) and current therapies.
PFK1↓, citrate promotes: - the inactivation of PFK1 and decreases ATP production [
ATP↓,
PFK2↓, inhibition of PFK2 in ascite cancer cells
Mcl-1↓, deactivation of the anti-apoptotic factor Mcl-1 and the activation of caspases such as caspase 2, 3 and 9
Casp3↑,
Casp2↑,
Casp9↑,
IGF-1R↓, downregulation of the IGF-1R/PI3K/AKT
PI3K↓,
Akt↓,
p‑Akt↓, decreased phosphorylation of AKT and ERK in non-small cell lung cancer
p‑ERK↓,
PTEN↑, activation of PTEN suppressor,
Snail↓, reversion of dedifferentiation (in particular through Snail inhibition with E-cadherin expression) and stimulation of T lymphocytes response
E-cadherin↑,
ChemoSen↑, increasing the sensitivity of tumors to cisplatin

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

1601- Cu,    The copper (II) complex of salicylate phenanthroline induces immunogenic cell death of colorectal cancer cells through inducing endoplasmic reticulum stress
- in-vitro, CRC, NA
i-CRT↓, Cu(sal)phen induced the release of calreticulin (CRT), adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1), the main molecular markers of ICD (immunogenic cell death)
ICD↑,
i-ATP↓,
i-HMGB1↓,
ER Stress↑, accumulation of ROS and inducing ERS
ROS↑,
DCells↑, promoted the maturation of dendritic cells (DCs)
CD8+↑, and activation of CD8+T cells
IL12↑, secretion of interleukin-12 (IL-12) and interferon-γ (IFN-γ)
IFN-γ↑,
TGF-β↓, while downregulating transforming growth factor-β (TGF-β) levels

2818- CUR,    Novel Insight to Neuroprotective Potential of Curcumin: A Mechanistic Review of Possible Involvement of Mitochondrial Biogenesis and PI3/Akt/ GSK3 or PI3/Akt/CREB/BDNF Signaling Pathways
- Review, AD, NA
*neuroP↑, Curcumin's protective functions against neural cell degeneration due to mitochondrial dysfunction and consequent events such as oxidative stress, inflammation, and apoptosis in neural cells have been documented
*ROS↓, studies show that curcumin exerts neuroprotective effects on oxidative stress.
*Inflam↓,
*Apoptosis↓,
*cognitive↑, cognitive performance to receive the title of neuroprotective
*cardioP↑, Studies have shown that curcumin can induce cell regeneration and defense in multiple organs such as the brain, cardiovascular system,
other↑, It has been shown that chronic use of curcumin in patients with neurodegenerative disorder can cause gray matter volume increase
*COX2↓, Curcumin also decreased the brain protein levels and activity of cyclooxygenase 2 (COX-2)
*IL1β↓, inhibition of IL-1β and TNF-α production, and enhancement of Nf-Kβ inhibition
*TNF-α↓,
NF-kB↓,
*PGE2↓, hronic curcumin therapy has shown a significant decrease in lipopolysaccharide (LPS)-induced elevation of brain prostaglandin E2 (PGE2) synthesis in rats
*iNOS↓, curcumin pretreatment decreased NOS activity in the ischemic rat model
*NO↓, curcumin has been shown to decrease NOS expression and NO production in rat brain tissue
*IL2↓, IL-2 is a cytokine that is anti-inflammatory. Numerous studies have shown that curcumin increases the secretion of IL-2
*IL4↓, curcumin reduced levels of IL-4
*IL6↓, Numerous studies have shown that curcumin in neurodegenerative events attenuates IL-6 production
*INF-γ↓, curcumin reduced the production of INF-γ, as pro-inflammatory cytokine
*GSK‐3β↓, Furthermore, previous findings have confirmed that inhibition of GSK-3β or CREB activation by curcumin has reduced the production of pro-inflammatory mediators under different conditions
*STAT↓, Inhibition of GSK-3β by curcumin has been found to result in reduced STAT activation
*GSH↑, chronic curcumin therapy increased glutathione levels in primary cultivated rat cerebral cortical cells
*MDA↓, multiple doses of 5, 10, 40 and 60 mg/kg) in rodents will inhibit neurodegenerative agent malicious effects, and reduce the amount of MDA and lipid peroxidation in brain tissue
*lipid-P↓,
*SOD↑, Curcumin induces increased production of SOD, glutathione peroxidase (GPx), CAT, and glutathione reductase (GR) activating antioxidant defenses
*GPx↑,
*Catalase↑,
*GSR↓,
*LDH↓, Curcumin decreased lactate dehydrogenase, lipoid peroxidation, ROS, H2O2 and inhibited Caspase 3 and 9
*H2O2↓,
*Casp3↓,
*Casp9↓,
*NRF2↑, ncreased mitochondrial uncoupling protein 2 and increased mitochondrial biogenesis. Nuclear factor-erythroid 2-related factor 2 (Nrf2)
*AIF↓, Curcumin treatment decreased the number of AIF positive nuclei 24 h after treatment in the hippocampus,
*ATP↑, curcumin in hippocampal cells induced an increase in mitochondrial mass leading to increased production of ATP with major improvements in mitochondrial efficiency

409- CUR,    Curcumin Inhibits Glyoxalase 1—A Possible Link to Its Anti-Inflammatory and Anti-Tumor Activity
- in-vitro, Pca, PC3 - in-vitro, BC, MDA-MB-231
GLO-I↓,
GSH↓, 50uM
ATP↓, mostly >50uM

951- DHA,    Docosahexaenoic Acid Attenuates Breast Cancer Cell Metabolism and the Warburg Phenotype by Targeting Bioenergetic Function
- in-vitro, BC, BT474 - in-vitro, BC, MDA-MB-231 - in-vitro, Nor, MCF10
Hif1a↓, in the malignant cell lines but not in the non-transformed cell line. ****
GLUT1↓, Downstream targets of HIF-1a, including glucose transporter 1 (GLUT 1) and lactate dehydrogenase (LDH), were decreased
LDH↓,
GlucoseCon↓,
lactateProd↓,
ATP↓, 50%
p‑AMPK↑,
ECAR↓, DHA significantly decreased basal ECAR by over 60%
OCR↓, basal OCR was decreased by 80%
*toxicity↓, while not affecting non-transformed MCF-10A cells

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↓,

5010- DSF,  Cu,  Rad,    Disulfiram/Copper Combined with Irradiation Induces Immunogenic Cell Death in Melanoma
- in-vivo, Melanoma, B16-F10
Apoptosis↑, DSF/Cu + IR significantly increased the cellular apoptosis and increased ICD markers:
ICD↑,
HMGB1↑, high-mobility group box 1 (HMGB1) release, and decreased intracellular ATP levels. I
ATP↓,
TumCG↓, DSF/Cu combined with IR treatment inhibited tumor growth and enhanced tumor-infiltrating immune cells in the B16F10-bearing C57BL/6 model

681- EGCG,    Suppressing glucose metabolism with epigallocatechin-3-gallate (EGCG) reduces breast cancer cell growth in preclinical models
- vitro+vivo, BC, NA
Casp3↑,
Casp8↑,
Casp9↑,
TumAuto↑,
Beclin-1↝,
ATG5↝,
GlucoseCon↓,
lactateProd↓,
ATP↝,
HK2↓, significantly inhibited the activities and mRNA levels of the glycolytic enzymes hexokinase (HK)
LDHA↓,
Hif1a↓,
GLUT1↓,
TumVol↓,
VEGF↓,

3241- EGCG,    Epigallocatechin gallate triggers apoptosis by suppressing de novo lipogenesis in colorectal carcinoma cells
- in-vitro, CRC, HCT116 - in-vitro, CRC, HT29 - in-vitro, Liver, HepG2 - in-vitro, Liver, HUH7
tumCV↓, EGCG treatment decreased cell viability and increased mitochondrial damage‐triggered apoptosis in both HCT116 and HT‐29 cancer cells
mtDam↑,
Apoptosis↑,
ATP↓, Suppression of ATP synthesis by EGCG
lipoGen↓, depletion of lipogenesis in the DNL pathway,
eff↑, Antiproliferative activity of EGCG and 5FU reduces tumor progression in a nude mouse xenograft model

1322- EMD,    The versatile emodin: A natural easily acquired anthraquinone possesses promising anticancer properties against a variety of cancers
- Review, Var, NA
Apoptosis↑,
TumCP↓,
ROS↑,
TumAuto↑,
EMT↓,
TGF-β↓,
DNAdam↑,
ER Stress↑,
TumCCA↑,
ATP↓,
NF-kB↓,
CYP1A1↑,
STAC2↓,
JAK↓,
PI3K↓,
Akt↓,
MAPK↓,
FASN↓,
HER2/EBBR2↓,
ChemoSen↑, DOX combined with emodin can improve the sensitivity of MDA-MB-231 and MCF-7 cells to chemotherapy
eff↑, emodin was reported to increase the anti-proliferative effect of an EGFR inhibitor (afatinib) against PC through downregulation of EGFR by promoting STAT3
ChemoSen↑, gemcitabine combined with emodin increased cell death
angioG↓,
VEGF↓,
MMP2↓,
eNOS↓,
FOXD3↑,
MMP9↓,
TIMP1↑,

5495- EP,    Irreversible electroporation in focal therapy for prostate cancer: current status and future directions
- Review, Pca, NA
Ca+2↑, Ca2+ overload→ATP depletion→mitochondrial dysfunction
ATP↓,
mtDam↑,
ROS↑, ROS generation from mitochondrial leakage disrupts cell homeostasis.
CellMemb↑, EP: membrane permeabilization→drug uptake↑;

4251- FA,    Antidepressant-Like Effect of Ferulic Acid via Promotion of Energy Metabolism Activity
- in-vivo, NA, NA
*BDNF↑, FA increases catecholamine (dopamine and noradrenaline), brain-derived neurotrophic factor, and ATP levels, and decreases glycogen levels in the limbic system of the mice brain.
*ATP↑,
*Mood↑, antidepressant-like effects of FA observed in this study

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

845- Gra,    A Review on Annona muricata and Its Anticancer Activity
- Review, NA, NA
GlucoseCon↓, decreased glucose absorption
ATP↓,
HIF-1↓,
GLUT1↓,
GLUT4↓,
HK2↓,
LDHA↓,
ERK↓,
Akt↓,
Apoptosis↑,
NF-kB↓,
ROS↑, increases ROS production
Bax:Bcl2↑,
MMP↓,
Casp3↑,
Casp9↑,
p‑JNK↓,

840- Gra,    Evaluation of cytotoxicity of aqueous extract of Graviola leaves on squamous cell carcinoma cell-25 cell lines by 3-(4,5-dimethylthiazol-2-Yl) -2,5-diphenyltetrazolium bromide assay and determination of percentage of cell inhibition at G2M phase of cell cycle by flow cytometry: An in vitro study
- in-vitro, SCC, SCC25
TumCCA↑, inhibition at G2M phase cell cycle
ATP↓, probable mechanism

836- Gra,    Graviola: A Novel Promising Natural-Derived Drug That Inhibits Tumorigenicity and Metastasis of Pancreatic Cancer Cells In Vitro and In Vivo Through Altering Cell Metabolism
- vitro+vivo, PC, NA
Hif1a↓,
NF-kB↓,
GLUT1↓,
GLUT4↓,
HK2↓,
LDHA↓,
TumCCA↑, G0/G1 cell cycle arrest
TumMeta↓,
GlucoseCon↓, 5%-20% of control for glucose uptake
ATP↓,
necrosis↑, cells incubated with Graviola extract have a gain in cell volume, a characteristic of necrotic cell death
Casp∅, Caspase-3 expression values remained statistically unaltered by treatment with the extract, suggesting that apoptotic pathways are not involved
p‑FAK↓,
MMP9↓,
MUC4↓, significant downregulation in MUC4

1232- Gra,    Graviola: A Systematic Review on Its Anticancer Properties
- Review, NA, NA
EGFR↓,
cycD1/CCND1↓,
Bcl-2↓,
TumCCA↑, G1 cell cycle arrest, 2nd ref :G0/G1 phase cell arrest
Apoptosis↑,
ROS↑,
MMP↓,
BAX↑,
Cyt‑c↑, cytochrome c release
Hif1a↓,
NF-kB↓,
GLUT1↓,
GLUT4↓,
HK2↓,
LDHA↓,
ATP↓,

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.

3767- H2,    The role of hydrogen therapy in Alzheimer's disease management: Insights into mechanisms, administration routes, and future challenges
- Review, AD, NA
*Inflam↓, Hydrogen therapy AD: inflammation, energy regulation, prevents neuronal damage.
*neuroP↑,
*toxicity↓, Hydrogen therapy's low side effects make it a complement to AD treatment. Even at high concentrations, hydrogen gas is still non-toxic, and has been widely used in the diving field.
*antiOx↑, hydrogen’s role as a natural antioxidant,
*ROS↓, Hydrogen has been shown to mitigate the amount of ROS released from mitochondria, thereby reducing mitochondrial DNA peroxidation and inhibiting the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), caspase-1, and I
*NLRP3↓,
*IL1β↓,
*mtDam↓, curtail mitochondrial damage, thereby bolstering ATP synthesis and fortifying the electron transport chain within mitochondria
*ATP↑,
*AMPK↑, activating AMPK and amplifying the downstream antioxidant response of forkhead box O3a (FOXO3
*FOXO3↑,
*SOD1↑, It elevates the levels of intracellular antioxidant enzymes, notably superoxide dismutase 1 (SOD1) and catalase (CAT), thereby serving as a neuroprotective agent that diminishes the risk and progression of AD
*Catalase↑,
*NRF2↑, Hydrogen slows AD progression by activating the cellular endogenous antioxidant system Nrf2;
*NO↓, Reduced inflammatory markers such as ROS, Nitric oxide (NO) and Malondialdehyde (MDA)
*MDA↓,
*lipid-P↓, drinking HRW significantly reduced lipid peroxidation in the brain of SAMP8 mice.
*memory↑, HRW inhibited the decline of learning and memory impairment
*ER(estro)↓, Decreased hormone levels, estrogen receptor (ER) β, and BDNF expression improve cognitive function in female transgenic AD mice.
*BDNF↑, upsurge in BDNF levels, which further ameliorated the cognitive impairments observed in mice affected by sepsis.
*cognitive↑,
*APP↓, The expression of APP, BACE1, and SAPPβ was proficiently suppressed, thereby curtailing the overproduction of Aβ in Alzheimer's
*BACE↓,
*Aβ↓,
*BP∅, inhaling hydrogen gas has no effect on blood pressure and other blood parameters (such as pH, body temperature, etc.),
*BBB↑, efficiently crossing the blood-brain barrier to perform their functions.

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

2879- HNK,    Honokiol Inhibits Lung Tumorigenesis through Inhibition of Mitochondrial Function
- in-vitro, Lung, H226 - in-vivo, NA, NA
tumCV↓, honokiol significantly reduced the percentage of bronchial that exhibit abnormal lung SCC histology from 24.4% bronchial in control to 11.0% bronchial in honokiol treated group (p= 0.01) while protecting normal bronchial histology (present in 20.5%
selectivity↑,
TumCP↓, In vitro studies revealed that honokiol inhibited lung SCC cells proliferation, arrested cells at the G1/S cell cycle checkpoint, while also leading to increased apoptosis.
TumCCA↑,
Apoptosis↑,
mt-ROS↑, interfering with mitochondrial respiration is a novel mechanism by which honokiol increased generation of reactive oxygen species (ROS) in the mitochondria, : mitochondrial ROS generation
Casp3↑, cells treated with honokiol showed a significant increase in caspase 3/7 activity, which occurred in dose- and time-dependent manners
Casp7↑,
OCR↓, Honokiol caused a fast and concentration-dependent decrease in basal oxygen consumption rate (OCR) in both cell lines
Cyt‑c↑, cytochrome c release was increased in honokil treated mouse lung SCC tissue
ATP↓, found a dramatic decrease in cellular ATP content
mitResp↓, Honokiol inhibits mitochondrial respiration and decreases ATP levels in H226 and H520 cells, which may elevate AMP and the intracellular AMP/ATP ratio, leading to activation of the AMPK
AMP↑,
AMPK↑,

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↑,

886- HPT,    Impact of hyper- and hypothermia on cellular and whole-body physiology
- Analysis, NA, NA
MMP↓,
OXPHOS↓, impaired oxidative phosphorylation
ATP↓,
ROS↑, increase reactive oxygen species (ROS) production within mitochondria,
Apoptosis↑,
Cyt‑c↑, releasing cytochrome c into the cytoplasm

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↓,

4292- LT,    Luteolin for neurodegenerative diseases: a review
- Review, AD, NA - Review, Park, NA - Review, MS, NA - Review, Stroke, NA
*Inflam↓, luteolin, showing significant anti-inflammatory, antioxidant, and neuroprotective activity.
*antiOx↑,
*neuroP↑,
*BioAv↝, To increase the bioavailability of luteolin, several delivery methods have been developed; the most thoroughly studied include lipid carriers like liposomes and nanoformulations
*BBB↑, luteolin given intraperitoneally (ip) to mice can readily cross the blood-brain barrier (BBB) and enter the brain
*TNF-α↓, nhibiting pro-inflammatory mediators such as cyclooxygenase-2 (COX-2), nitric oxide (NO), TNF-α, IL-β, IL-6, IL-8, IL-31, and IL-33 in several in vitro models of AD
*IL1β↓,
*IL6↓,
*IL8↓,
*IL33↓,
*NF-kB↓, inhibition of the NF-кB pathway
*BACE↓, leads to the inhibition of a downstream target– β-site amyloid precursor protein cleaving enzyme (BACE1), which is a key mediator in forming Aβ fibrils in AD pathology
*ROS↓, anti-oxidant activity mainly by reducing ROS levels and increasing SOD activity in in vitro models of AD
*SOD↑,
*HO-1↑, increase the expression of antioxidant enzymes such as heme oxygenase-1 (HO-1) via the nuclear factor erythroid 2–related factor 2/ antioxidant responsive element (Nrf-2/ARE) complex activation
*NRF2↑,
*Casp3↓, reducing the levels of caspase-3 and − 9 and improving the B-cell lymphoma protein 2/Bcl-2-associated X protein (Bcl-2/Bax) ratio, as it was reported in in vitro models of AD
*Casp9↑,
*Bax:Bcl2↓,
*UPR↑, enhancing the unfolded protein response (UPR) pathway, leading to an increase in endoplasmic reticulum (ER) chaperone GRP78 and a decrease in the expression of UPR-targeted pro-apoptotic genes via the MAPK pathway.
*GRP78/BiP↑,
*Aβ↓, evidence that suggests that luteolin can directly influence the formation of Aβ plaques by selectively inhibiting the activity of N-acetyl-α-galactosaminyltransferase (ppGalNAc-T) isoforms
*GSK‐3β↓, inactivating the glycogen synthase kinase-3 alpha (GSK-3α) isoform, suppressing Aβ and promoting tau disaggregation
*tau↓,
*CREB↑, luteolin promoted phosphorylation and activation of cAMP response element-binding protein (CREB) leading to the increased miR-132 expression, and eventually neurite outgrowth in PC12 cells
*ATP↑, ROS production was decreased by 40%, MMP levels were restored close to control N2a levels (202%), and ATP levels were improved by 444%).
*cognitive↑, protective effect of luteolin against cognitive dysfunction was also reported in the streptozotocin
*BloodF↑, Luteolin increased regional cerebral blood flow values, alleviated the leakage of the lumen of vessels, and protected the integrity of BBB
*BDNF↑, increasing the level of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor (TrkB) expression in the cerebral cortex
*TrkB↑,
*memory↑, luteolin supplementation significantly ameliorated memory and cognitive deficits in 3 × Tg-AD mice.
*PPARγ↑, attenuated mitochondrial dysfunction via peroxisome proliferator-activated receptor gamma (PPARγ) activation.
*eff↑, combination of luteolin with another compound– l-theanine (an amino acid found in tea) also improved AD-like symptoms in the Aβ25–35-treated rats

2913- LT,    Luteolin induces apoptosis by impairing mitochondrial function and targeting the intrinsic apoptosis pathway in gastric cancer cells
- in-vitro, GC, HGC27 - in-vitro, BC, MCF-7 - in-vitro, GC, MKN45
TumCP↓, Luteolin inhibited the proliferation of gastric cancer HGC-27, MFC and MKN-45 cells
MMP↓, impaired mitochondrial integrity and function by destroying the mitochondrial membrane potential,
Apoptosis↑, eventually leading to apoptosis of gastric cancer HGC-27, MFC and MKN-45 cells
ROS↑, luteolin-induced ROS accumulation in HGC-27, MFC and MKN-45 cells. HGC-27 and MFC cells were treated with luteolin (10, 40, and 70 µM) for 24 h, and MKN-45 cells were treated for 48 h
SOD↓, suggested that luteolin could induce SOD activity reduction, especially in the high dose of luteolin groups in HGC-27 and MFC cells
ATP↓, ATP content decreased, especially in the high-dose groups
Bax:Bcl2↑, luteolin significantly decreased the ratio between Bcl-2 and Bax in HGC-27, MFC, and MKN-45 cells
TumCCA↑, In addition, it is reported that luteolin could induce cell cycle arrest and apoptosis through extrinsic and intrinsic signaling pathways in MCF-7 breast cancer cell

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)

2643- MCT,    Medium Chain Triglycerides enhances exercise endurance through the increased mitochondrial biogenesis and metabolism
- Review, Nor, NA
*Akt↑, increased mitochondrial biogenesis and metabolism is mediated through the activation of Akt and AMPK signaling pathways and inhibition of TGF-β signaling pathway.
*AMPK↓,
*TGF-β↓, MCT downregulates TGF-β signaling
eff↑, beneficial effect of dietary MCT in exercise performance through the increase of mitochondrial biogenesis and metabolism.
*BioEnh↑, Furthermore, addition of the combination of chilli and MCT to meals increased diet-induced thermogenesis by over 50% in heathy normal-weight humans
*ATP↑, a key regulator of energy metabolism and mitochondrial membrane ATP synthase (ATP5α) were significantly upregulated by MCT.
*PGC-1α↑, also observed a significant increase in protein level of PGC-1α and ATP5α
*p‑mTOR↑, increased levels in both total and phosphorylated Akt and mTOR
*SMAD3↓, a compensatory response of the huge reduction in Smad3.

1780- MEL,    Utilizing Melatonin to Alleviate Side Effects of Chemotherapy: A Potentially Good Partner for Treating Cancer with Ageing
- Review, Var, NA
*antiOx↑, Melatonin is a potent antioxidant and antiageing molecule, is nontoxic, and enhances the efficacy and reduces the side effects of chemotherapy.
*toxicity↓,
ChemoSen↑,
*eff↑, melatonin was superior in preventing free radical destruction compared to other antioxidants, vitamin E, β-carotene, vitamin C, and garlic oil
*mitResp↑, increasing the expression and activity of the mitochondrial respiration chain complexes
*ATP↑, increasing the expression and activity of the mitochondrial respiration chain complexes
*ROS↓, most attractive property of melatonin is that its metabolites also regulate the mitochondrial redox status by scavenging ROS and RNS
*CardioT↓, melatonin has a protective effect on the heart without affecting DOX's antitumor activity,
*GSH↑, improving the de novo synthesis of glutathione (GSH) by promoting the activity of gamma-glutamylcysteine synthetase
*NOS2↓, melatonin inhibits the production of nitric oxide synthase (NOS)
*lipid-P↓, lipid peroxidation was reduced after melatonin treatment (role in induces organ failure)
eff↑, but it also enhances its antitumor activity more than vitamin E
*HO-1↑, melatonin upregulates heme oxygenase-1 (HO-1) (role in induces organ failure)
*NRF2↑, decreased bladder injury and apoptosis due to the upregulation of Nrf2 and nuclear transcription factor NF-κB expression
*NF-kB↑,
TumCP↓, significantly reduced cell proliferation
eff↑, Pretreatment with melatonin effectively preserved the ovaries from cisplatin-induced injury
neuroP↑, Melatonin has neuroprotective roles in oxaliplatin-induced peripheral neuropathy

1778- MEL,    Melatonin: a well-documented antioxidant with conditional pro-oxidant actions
- Review, Var, NA - Review, AD, NA
*ROS↓, melatonin and its metabolic derivatives possess strong free radical scavenging properties.
*antiOx↓, potent antioxidants against both ROS (reactive oxygen species) and RNS (reactive nitrogen species). reduce oxidative damage to lipids, proteins and DNA under a very wide set of conditions where toxic derivatives of oxygen are known to be produced.
ROS↑, a few studies using cultured cells found that melatonin promoted the generation of ROS at pharmacological concentrations (μm to mm range) in several tumor and nontumor cells; thus, melatonin functioned as a conditional pro-oxidant.
selectivity↑, melatonin functions as a prooxidant in cancer cells where it aids in the killing of tumor cells
Dose↑, Melatonin levels in the nucleus and mitochondria reached saturation with a lower dose of 40 mg/kg body weight, with no further accumulation under higher doses of injected melatonin
*mitResp↑, improves mitochondrial respiration and ATP production, thereby reducing electron leakage and ROS generation
*ATP↑,
*ROS↓,
eff↑, melatonin protects mitochondrial function in the brain of Alzheimer's patients through both MT1/MT2 dependent and independent mechanisms
ROS↑, Cytochrome P450 utilizes melatonin as a substrate to generate ROS in mitochondria (melatonin concentration ranges from 0.1 to 10 uM)
Dose↑, melatonin at high concentrations (10-1000uM ) was able to promote ROS generation and lead to Fas-induced apoptosis in human leukemic Jurkat cells. Concentrations of <10uM , melatonin did not induce significant ROS generation in these cancer cells
*toxicity∅, High levels of melatonin (uM to mM) did not cause cytotoxicity in several types of nontumor cells
ROS↑, lower concentrations of melatonin (0.1-10uM ), which exhibited antioxidant action in HepG2 cells within 24 hr, became pro-oxidant after 96 hr of treatment, as indicated by the increase of GSH with 24hr and depletion after 96 hr.
eff↓, Finally, a compound, chlorpromazine, which specifically interrupts the binding of melatonin to calmodulin [188], prevented melatonin-induced AA release and ROS generation;
ROS↝, It remains unknown whether the pro-oxidant action exists in vivo. the vast majority of evidence indicates that melatonin is a potent antioxidant in vivo even at pharmacological concentrations
Dose↑, decline of melatonin production with age may render it more beneficial to supplement melatonin to the aging population to improve health by reducing free radical damage
other↑, melatonin intake has the potential to improve cardiac function, inhibit cataract formation, maintain brain health, alleviate metabolic syndrome, obesity and diabetes,reduce tumorigenesis, protect tissues against ischemia

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↑,

2457- MET,    Metformin Impairs Glucose Consumption and Survival in Calu-1 Cells by Direct Inhibition of Hexokinase-II
- in-vitro, Lung, Calu-1
HK1↓, Here we show that metformin impairs the enzymatic function of HKI and II in Calu-1 cells.
HK2↓,
GlucoseCon↓, This inhibition virtually abolishes cell glucose uptake
MMP↓, results in mitochondrial depolarization and subsequent cell death
ATP↓, Metformin effects resulted in a marked and dose-dependent increase in the AMP/ATP ratio

2242- MF,    Electromagnetic stimulation increases mitochondrial function in osteogenic cells and promotes bone fracture repair
- in-vitro, Nor, NA
*MMP↑, we show that application of a low intensity constant EM field source on osteogenic cells in vitro resulted in increased mitochondrial membrane potential and respiratory complex I activity and induced osteogenic differentiation.
*Diff↑,
*OXPHOS↑, effect was mediated via increased OxPhos activity
*BMD↑, EM field source enhanced fracture repair via improved biomechanical properties and increased callus bone mineralization
ATP∅, higher mitochondrial OxPhos activity leads to higher ATP production, increased cellular activity leads to increased ATP consumption.

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

538- MF,    The extremely low frequency electromagnetic stimulation selective for cancer cells elicits growth arrest through a metabolic shift
- in-vitro, BC, MDA-MB-231 - in-vitro, Melanoma, MSTO-211H
TumCG↓, did not affect the non-malignant counterpart.
Ca+2↑,
COX2↓,
ATP↑, (ATP5B) and mitochondrial transcription (MT-ATP6)
MMP↑, significant enhancement of mitochondrial membrane potential (ΔΨm)
ROS↑, demonstrated for the first time the association of ROS production with the stimulation of the mitochondrial metabolism triggered by the electromagnetic field
OXPHOS↑,
mitResp↑, Mitochondrial respiration is increased by ELF-EMF exposure

531- MF,    6-mT 0-120-Hz magnetic fields differentially affect cellular ATP levels
- in-vitro, Cerv, HeLa - in-vitro, CRC, HCT116 - in-vitro, BC, MCF-7 - in-vitro, Lung, A549 - in-vitro, Nor, RPE-1 - in-vitro, Nor, GP-293
ATP⇅, variable effects

537- MF,  immuno,    Integrating electromagnetic cancer stress with immunotherapy: a therapeutic paradigm
- Review, Var, NA
Apoptosis↑,
ROS↑,
TumAuto↑,
Ca+2↑, Ca++ ion tumor-cell entry
ATP↓, ATP depletion
eff↑, In physical terms, the rate of rise in a magnetic pulse or oscillation (i.e., its “sharpness”) is conveyed as dB/dt). The EMF induced by that particular period of rise to the maximum amplitude may be more impactful on unique tumor cellular features
eff↑, The induction intensity (dB/dt) may well be more critical than the field maximum amplitude (B max) in this setting

493- MF,    Extremely low-frequency electromagnetic field induces acetylation of heat shock proteins and enhances protein folding
- in-vitro, NA, HEK293 - in-vitro, Liver, AML12
ATP↑,
HSP70/HSPA5↓, however, acetylations of HSP70 and HSP90 were increased
HSP90↓, however, acetylations of HSP70 and HSP90 were increased

3477- MF,    Electromagnetic fields regulate calcium-mediated cell fate of stem cells: osteogenesis, chondrogenesis and apoptosis
- Review, NA, NA
*Ca+2↑, When cells are subjected to external mechanical stimulation, voltage-gated ion channels in the cell membrane open and intracellular calcium ion concentration rises
*VEGF↑, BMSCs EMF combined with VEGF promote osteogenesis and angiogenesis
*angioG↑,
Ca+2↑, 1 Hz/100 mT MC4-L2 breast cancer cells EMF lead to calcium ion overload and ROS increased, resulting in necroptosis
ROS↑,
Necroptosis↑,
TumCCA↑, 50 Hz/4.5 mT 786-O cells ELF-EMF induce G0/G1 arrest and apoptosis in cells lines
Apoptosis↑,
*ATP↑, causing the ATP or ADP increases, and the purinergic signal can upregulate the expression of P2Y1 receptors
*FAK↑, Our research team [53] found that ELE-EMF can induce calcium oscillations in bone marrow stem cells, up-regulated calcium ion activates FAK pathway, cytoskeleton enhancement, and migration ability of stem cells in vitro is enhanced.
*Wnt↑, ability of EMF to activate the Wnt10b/β-catenin signaling pathway to promote osteogenic differentiation of cells depends on the functional integrity of primary cilia in osteoblasts.
*β-catenin/ZEB1↑,
*ROS↑, we hypothesize that the electromagnetic field-mediated calcium ion oscillations, which causes a small amount of ROS production in mitochondria, regulates the chondrogenic differentiation of cells, but further studies are needed
p38↑, RF-EMF was able to suppress tumor stem cells by activating the CAMKII/p38 MAPK signaling pathway after inducing calcium ion oscillation and by inhibiting the β-catenin/HMGA2 signaling pathway
MAPK↑,
β-catenin/ZEB1↓,
CSCs↓, Interestingly, the effect of electromagnetic fields is not limited to tumor stem cells, but also inhibits the proliferation and development of tumor cells
TumCP↓,
ROS↑, breast cancer cell lines exposed to ELE-EMF for 24 h showed a significant increase in intracellular ROS expression and an increased sensitivity to further radiotherapy
RadioS↑,
Ca+2↑, after exposure to higher intensity EMF radiation, showed a significant increase in intracellular calcium ion and reactive oxygen species, which eventually led to necroptosis
eff↓, while this programmed necrosis of tumor cells was able to be antagonized by the calcium blocker verapamil or the free radical scavenger n -acetylcysteine
NO↑, EMF can regulate multiple ions in cells, and calcium ion play a key role [92, 130], calcium ion acts as a second messenger that can activate downstream molecules such as NO, ROS

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↑,

4355- MF,    Ambient and supplemental magnetic fields promote myogenesis via a TRPC1-mitochondrial axis: evidence of a magnetic mitohormetic mechanism
- in-vitro, Nor, C2C12
*mt-OCR↑, figure 1
*mt-ROS↑, Exposure to PEMFs stimulated the production of ROS (Fig. 6A, B) and ATP
*ECAR↑, figure 6
*Dose↝, barrages of 20 × 150 μs on and off pulses for 6 ms repeated at a frequency of 15 Hz. The magnetic flux density rose to predetermined maximal level within ∼50 μs (∼17 T/s) when driving field amplitudes between 0.5 and 3 mT.
*Ca+2↑, 10 min) of C2C12 myoblasts to PEMFs (Supplemental Fig. S1A) augmented cytosolic calcium levels [intracellular [Ca2+] concentration ([Ca2+]i), blue] relative to unexposed myoblasts
*ATP↑,
*other↑, PEMF-stimulated proliferation of myoblasts
*eff↓, TRPC1 silencing precludes PEMF sensitivity.
*eff↝, revealed a magnetic efficacy window

773- Mg,    Methyl Jasmonate-induced Increase in Intracellular Magnesium Promotes Apoptosis in Breast Cancer Cells
- in-vitro, BC, MCF-7
TRPM7↓, increase in [Mg2+]i led to decreased TRPM7 expression
ROS↑,
ER Stress↑,
MAPK↑,
ATP↓,

1891- MGO,    Methylglyoxal induces mitochondria-dependent apoptosis in sarcoma
- in-vitro, SCC, NA
NADH↓, It appears that this specificity of methylglyoxal against the NADH dehydrogenase (complex I) of malignant tissue mitochondria is one very important reason for its selective anticancer property.
MMP↓, decrease in membrane potential
Cyt‑c↑, Release of cytochrome c from sarcoma tissue mitochondria.
selectivity↑, The results presented in this and the preceding paper clearly indicate that action of methylglyoxal is selective against malignant cells
Apoptosis↑, Methylglyoxal showed cytotoxicity to several malignant cells through induction of apoptosis
ROS↑, It was previously reported that methylglyoxal induced ROS generation triggered apoptosis in human Hep G2 cells
ATP↓, ATP deprivation

2451- PA,    The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors
- Review, Var, NA
HK2↓, PA was found to significantly inhibit HK II activity in cell lysates (IC50 5.01 μm), induce mitochondrial dysfunction, ATP depletion, and ROS generation.
ATP↓,
ROS↑,

2452- PA,    Targeting Pyruvate Kinase M2 and Hexokinase II, Pachymic Acid Impairs Glucose Metabolism and Induces Mitochondrial Apoptosis
- in-vitro, BC, SkBr3
HK2↓, Molecular docking and enzyme assay confirmed that PA was an inhibitor of HK2, with an IC50 of 5.01 µM.
GlucoseCon↓, PA decreased glucose uptake and lactate production
lactateProd↓,
mtDam↑, PA induced mitochondrial dysfunction, ATP depletion, and ROS generation
ATP↓,
ROS↑,
PKM2↑, The activation of PKM2 should have increased the uptake of glucose and production of lactate. However, opposite results were obtained in this study

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.

2430- PBG,    The cytotoxic effects of propolis on breast cancer cells involve PI3K/Akt and ERK1/2 pathways, mitochondrial membrane potential, and reactive oxygen species generation
- in-vitro, BC, MDA-MB-231
TumCP↓, CP extract exhibited antiproliferative and cytotoxic effects on MDA MB-231 cells, what may be probably related to PI3K/Akt and ERK1/2 pathways.
TP53↓, decreased expression of apoptosis-related genes (TP53, CASP3, BAX and P21)
Casp3↓,
BAX↓,
P21↓,
ROS↑, These results suggested that CP cytotoxic effects on MDA MB-231 cells might be associated with the intracellular ROS production
eff↓, CP-induced ROS generation was reduced after cotreatment with the antioxidant NAC, which increased the percentage of viable cells, suggesting that CP-induced necrotic-related cell death could be associated with ROS production
MMP↓, Necrosis death is associated with mitochondrial dysfunction and our propolis sample reduced the MMP and increased LDH levels.
LDH↑,
ATP↓, rupture of mitochondrial membrane, loss of adenosine triphosphate (ATP),
Ca+2↑, excessive ROS production, intracellular [Ca+2] elevation, osmotic shock,

4946- PEITC,    Phenethyl Isothiocyanate Inhibits Oxidative Phosphorylation to Trigger Reactive Oxygen Species-mediated Death of Human Prostate Cancer Cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, PC3
Apoptosis↑, inhibits growth of human cancer cells by causing apoptotic and autophagic cell death.
TumAuto↑,
ROS↑, we demonstrate that the PEITC-induced cell death is initiated by production of reactive oxygen species (ROS) resulting from inhibition of oxidative phosphorylation (OXPHOS)
OXPHOS↓,
ATP↓, , suppression of OXPHOS, and ATP depletion.
selectivity↑, These effects were not observed in a representative normal human prostate epithelial cell line (PrEC)
ETC↓, PEITC-induced cell death involving ROS production due to inhibition of complex III and OXPHOS.
eff↓, PEITC-mediated increase in CM· signal intensity in PC-3 cells was markedly suppressed in the presence of NAC
eff↓, Rho-0 Variants of LNCaP and PC-3 Cells Were Resistant to PEITC-induced Apoptosis
BAX↑, PEITC Treatment Caused Mitochondrial Translocation of Bax

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

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.

3350- QC,    Quercetin and the mitochondria: A mechanistic view
- Review, NA, NA
*antiOx↑, antioxidant and anti-inflammatory properties
*Inflam↓,
*NRF2↑, Quercetin is able to activate the master regulator nuclear factor erythroid 2-related factor 2 (Nrf2)
ROS⇅, That is, as a free radical-scavenging antioxidant, quercetin protects cells against DNA damage induced by reactiveoxygen species (ROS), but the oxidized quercetin intermediates (see above) can then react with glutathione (GSH) thereby lowering GSH
*NRF2↑, 10uM (24 h) Mouse primary hepatocytes Activation of Nrf2; ↑HO-1 levels; ↑expression of PPARα and PGC-1α
*HO-1↑,
*PPARα↑,
*PGC-1α↑,
*SIRT1↑, Rat hippocampus ↑ SIRT1, PGC-1α, NRF-1, and TFAM levels; ATP levels;
*ATP↑,
ATP↓, L1210 and P388 leukemia cells (Suolinna et al., 1975). At least in part, the authors attributed the pro-apoptotic effect of quercetin in these cell lines to its capacity to inhibit ATP synthase, causing a decrease in ATP content.
ERK↓, downregulation of ERK1/2 by quercetin (50-100 uM for 24 or 48 h, combined or not with resveratrol
cl‑PARP↑, NCaP cells ↑PARP cleavage ↑ Caspase-9, caspase-8, and caspase-3 activities
Casp9↑,
Casp8↑,
BAX↑, MDA-MB-231 cells ↑Bax levels, ↓MMP, ↑cytochrome c release, ↑caspase-9 and caspase-3 activities
MMP↓,
Cyt‑c↑,
Casp3↑,
HSP27↓, T98G cells: ↓Hsp27 and Hsp72 contents, ↓Ras and Raf level
HSP72↓,
RAS↓,
Raf↓,

3336- QC,    Neuroprotective Effects of Quercetin in Alzheimer’s Disease
- Review, AD, NA
*neuroP↑, Neuroprotection by quercetin has been reported in several in vitro studies
*lipid-P↓, It has been shown to protect neurons from oxidative damage while reducing lipid peroxidation.
*antiOx↑, In addition to its antioxidant properties, it inhibits the fibril formation of amyloid-β proteins, counteracting cell lyses and inflammatory cascade pathways.
*Aβ↓,
*Inflam↓,
*BBB↝, It also has low BBB penetrability, thus limiting its efficacy in combating neurodegenerative disorders.
*NF-kB↓, downregulating pro-inflammatory cytokines, such as NF-kB and iNOS, while stimulating neuronal regeneration
*iNOS↓,
*memory↑, Quercetin has shown therapeutic efficacy, improving learning, memory, and cognitive functions in AD
*cognitive↑,
*AChE↓, Quercetin administration resulted in the inhibition of AChE
*MMP↑, quercetin ameliorates mitochondrial dysfunction by restoring mitochondrial membrane potential, decreases ROS production, and restores ATP synthesis
*ROS↓,
*ATP↑,
*AMPK↑, It also increased the expression of AMP-activated protein kinase (AMPK), which is a key cell regulator of energy metabolism.
*NADPH↓, Activated AMPK can decrease ROS generation by inhibiting NADPH oxidase activity
*p‑tau↓, Inhibition of AβAggregation and Tau Phosphorylation

39- QC,    A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells
- Analysis, NA, NA
ROS↑, production of ROS in both cancer, and cancer stem cells,
GSH↓, By directly reducing the intracellular pool of glutathione (GSH), QC can influence ROS metabolism
IL6↓, QC is its ability to inhibit inflammatory mediators including IFN-γ, IL-6, COX-2, IL-8, iNOS, TNF-α, and many other cancer inflammatory mechanisms
COX2↓,
IL8↓,
iNOS↓,
TNF-α↓,
MAPK↑, quercetin-3-methyl ether stopped the growth of cancer in the esophagus by blocking the Akt/mTOR/P70S6k and MAPK pathways, which are important for the growth of cancer
ERK↑,
SOD↑,
ATP↓,
Casp↑,
PI3K/Akt↓,
mTOR↓,
NOTCH1↓,
Bcl-2↓,
BAX↑,
IFN-γ↓,
TumCP↓, QC directly involves inducing apoptosis and/or the cell cycle arrest process, and also inhibits the propagation of rapidly proliferating cells
TumCCA↑,
Akt↓, quercetin-3-methyl ether stopped the growth of cancer in the esophagus by blocking the Akt/mTOR/P70S6k and MAPK pathways, which are important for the growth of cancer
P70S6K↓,
*Keap1↓,
*GPx↑, inhibiting its negative regulator, Keap1, resulting in Nrf-2 nuclear translocation [86]. This results in the production and activation of enzymes namely GPX, CAT, heme oxygenase 1 (HO-1), peroxiredoxin (PRX)
*Catalase↑,
*HO-1↑,
*NRF2↑,
NRF2↑, The effect of QC on nuclear translocation of Nrf-2 in a time-dependent manner, and increased expression level in HepG2, MgM (malignant mesothelioma) MSTO-211H, and H2452 cells at mRNA and protein quantity has been reported recently
eff↑, quercetin coupled with gold nanoparticles promoted apoptosis by inhibiting the EGFR/P13K/Akt-mediated pathway
HIF-1↓, Quercetin has been shown to suppress the Akt-mTOR pathway and hypoxia-induced factor 1 signaling pathway in gastric cancer cells, resulting in preventative autophagy

889- QC,    The multifaceted role of quercetin derived from its mitochondrial mechanism
- vitro+vivo, Var, NA
MMP↓,
ATP↝,
OXPHOS↝,
ROS↑, a prooxidant effect

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↓,

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.

2566- RES,    A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke
- Review, Stroke, NA
*neuroP↑, comprehensive overview of resveratrol's neuroprotective role in IS
*NRF2↑, Findings from previous studies suggest that Nrf2 activation can significantly reduce brain injury following IS and lead to better outcomes
*SIRT1↑, neuroprotective effects by activating nuclear factor erythroid 2-related factor 2 (NRF2) and sirtuin 1 (SIRT1) pathways.
*PGC-1α↑, IRT1 activation by resveratrol triggers the deacetylation and activation of downstream targets like peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) and forkhead box protein O (FOXO)
*FOXO↑,
*HO-1↑, ctivation of NRF2 through resveratrol enhances the expression of antioxidant enzymes, like heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1), which neutralize reactive oxygen species and mitigate oxidative stress in the ischemic bra
*NQO1↑,
*ROS↓,
*BP↓, Multiple studies have demonstrated that resveratrol presented protective effects in IS, it can mediate blood pressure and lipid profiles which are the main key factors in managing and preventing stroke
*BioAv↓, The residual quantity of resveratrol undergoes metabolism, with the maximum reported concentration of free resveratrol being 1.7–1.9 %
*Half-Life↝, The levels of resveratrol peak 60 min following ingestion. Another study found that within 6 h, there was a further rise in resveratrol levels. This increase can be attributed to intestinal recirculation of metabolites
*AMPK↑, Resveratrol also increases AMPK and inhibits GSK-3β (glycogen synthase kinase 3 beta) activity in astrocytes, which release energy, makes ATP available to neurons and reduces ROS
*GSK‐3β↓,
*eff↑, Furthermore, oligodendrocyte survival is boosted by resveratrol, which may help to preserve brain homeostasis following a stroke
*AntiAg↑, resveratrol may suppress platelet activation and aggregation caused by collagen, adenosine diphosphate, and thrombin
*BBB↓, Although resveratrol is a highly hydrophobic molecule, it is exceedingly difficult to penetrate a membrane like the BBB. However, an alternate administration is through the nasal cavity in the olfactory area, which results in a more pleasant route
*Inflam↓, Resveratrol's anti-inflammatory effects have been demonstrated in many studies
*MPO↓, Resveratrol dramatically lowered the amounts of cerebral infarcts, neuronal damage, MPO activity, and evans blue (EB) content in addition to neurological impairment scores.
*TLR4↓, TLR4, NF-κB p65, COX-2, MMP-9, TNF-α, and IL-1β all had greater levels of expression after cerebral ischemia, whereas resveratrol decreased these amounts
*NF-kB↓,
*p65↓,
*MMP9↓,
*TNF-α↓,
*IL1β↓,
*PPARγ↑, Previous studies have shown that resveratrol activates the PPAR -γ coactivator 1α (PGC-1 α), which has free radical scavenging properties
*MMP↑, Resveratrol can prevent mitochondrial membrane depolarization, preserve adenosine triphosphate (ATP) production, and inhibit the release of cytochrome c
*ATP↑,
*Cyt‑c∅,
*mt-lipid-P↓, mitochondrial lipid peroxidation (LPO), protein carbonyl, and intracellular hydrogen peroxide (H2O2) content were significantly reduced in the resveratrol treatment group, while the expression of HSP70 and metallothionein were restored
*H2O2↓,
*HSP70/HSPA5↝,
*Mets↝,
*eff↑, Shin et al. showed that 5 mg/kg intravenous (IV) resveratrol reduced infarction volume by 36 % in an MCAO mouse model.
*eff↑, This study indicates that resveratrol holds the potential to improve stroke outcomes before ischemia as a pre-treatment strategy
*motorD↑, resveratrol treatment significantly reduced infarct volume and prevented motor impairment, increased glutathione, and decreased MDA levels compared to the control group,
*MDA↓,
*NADH:NAD↑, Resveratrol treatment significantly enhanced the intracellular NAD+/NADH ratio
eff↑, Pretreatment with resveratrol (20 or 40 mg/kg) significantly lowered the cerebral edema, infarct volume, lipid peroxidation products, and inflammatory markers
eff↑, Intraperitoneal administration of resveratrol at a dose of 50 mg/kg reduced cerebral ischemia reperfusion damage, brain edema, and BBB malfunction

3092- RES,    Resveratrol in breast cancer treatment: from cellular effects to molecular mechanisms of action
- Review, BC, MDA-MB-231 - Review, BC, MCF-7
TumCP↓, The anticancer mechanisms of RES in regard to breast cancer include the inhibition of cell proliferation, and reduction of cell viability, invasion, and metastasis.
tumCV↓,
TumCI↓,
TumMeta↓,
*antiOx↑, antioxidative, cardioprotective, estrogenic, antiestrogenic, anti-inflammatory, and antitumor properties it has been used against several diseases, including diabetes, neurodegenerative diseases, coronary diseases, pulmonary diseases, arthritis, and
*cardioP↑,
*Inflam↓,
*neuroP↑,
*Keap1↓, RES administration resulted in a downregulation of Keap1 expression, therefore, inducing Nrf2 signaling, and leading to a decrease in oxidative damage
*NRF2↑,
*ROS↓,
p62↓, decrease the severity of rheumatoid arthritis by inducing autophagy via p62 downregulation, decreasing the levels of interleukin-1β (IL-1β) and C-reactive protein as well as mitigating angiopoietin-1 and vascular endothelial growth factor (VEGF) path
IL1β↓,
CRP↓,
VEGF↓,
Bcl-2↓, RES downregulates the levels of Bcl-2, MMP-2, and MMP-9, and induces the phosphorylation of extracellular-signal-regulated kinase (ERK)/p-38 and FOXO4
MMP2↓,
MMP9↓,
FOXO4↓,
POLD1↓, The in vivo experiment involving a xenograft model confirmed the ability of RES to reduce tumor growth via POLD1 downregulation
CK2↓, RES reduces the expression of casein kinase 2 (CK2) and diminishes the viability of MCF-7 cells.
MMP↓, Furthermore, RES impairs mitochondrial membrane potential, enhances ROS generation, and induces apoptosis, impairing BC progression
ROS↑,
Apoptosis↑,
TumCCA↑, RES has the capability of triggering cell cycle arrest at S phase and reducing the number of 4T1 BC cells in G0/G1 phase
Beclin-1↓, RES administration promotes cytotoxicity of DOX against BC cells by downregulating Beclin-1 and subsequently inhibiting autophagy
Ki-67↓, Reducing the Ki-67
ATP↓, RES’s administration is responsible for decreasing ATP production and glucose metabolism in MCF-7 cells.
GlutMet↓,
PFK↓, RES decreased PFK activity, preventing glycolysis and glucose metabolism in BC cells and decreasing cellular growth rate
TGF-β↓, RES (12.5–100 µM) inhibited TGF-β signaling and reduced the expression levels of its downstream targets that include Smad2 and Smad3 and as a result impaired the progression of BC cells.
SMAD2↓,
SMAD3↓,
Vim?, a significant decrease in the levels of vimentin, Snail1 and Slug occurred, while E-cadherin levels increased to suppress EMT and metastasis of BC cells.
Snail↓,
Slug↓,
E-cadherin↑,
EMT↓,
Zeb1↓, a significant decrease in the levels of vimentin, Snail1 and Slug occurred, while E-cadherin levels increased to suppress EMT and metastasis of BC cells.
Fibronectin↓,
IGF-1↓, RES administration (10 and 20 µM) impaired the migration and invasion of BC cells via inhibiting PI3K/Akt and therefore decreasing IGF-1 expression and preventing the upregulation of MMP-2
PI3K↓,
Akt↓,
HO-1↑, The activation of heme oxygenase-1 (HO-1) signaling by RES reduced MMP-9 expression and prevented metastasis of BC cells
eff↑, RES-loaded gold nanoparticles were found to enhance RES’s ability to reduce MMP-9 expression as compared to RES alone
PD-1↓, RES inhibited PD-1 expression to promote CD8+ T cell activity and enhance Th1 immune responses.
CD8+↑,
Th1 response↑,
CSCs↓, RES has the ability to target CSCs in various tumors
RadioS↑, RES in reversing drug resistance and radio resistance.
SIRT1↑, RES administration (12.5–200 µmol/L) promotes sensitivity of BC cells to DOX by increasing Sirtuin 1 (SIRT1) expression
Hif1a↓, downregulating HIF-1α expression, an important factor in enhancing radiosensitivity
mTOR↓, mTOR suppression

1490- RES,    Anticancer Potential of Resveratrol, β-Lapachone and Their Analogues
- Review, Var, NA
TumCCA↑, lapachone and its iodine derivatives induce cell cycle arrest in G2/M in human oral squamous cell carcinoma cells
ROS↑, The primary mechanism of action of β-lapachone and its derivatives is the formation of ROS [92] through its processing by NAD(P)H quinone oxidoreductase 1 (NQO1).
Ca+2↑, abnormal production of ROS leads to an increase in Ca++
MMP↓, depolarization of the mitochondrial membrane
ATP↓, decrease in ATP synthesis
TOP1?, β-lapachone inhibits the catalytic activity of topoisomerase I
P53↑, including upregulation of the p53 tumor suppressor protein
p53 Wildtype∅,
Akt↓, inactivation of the Akt/mTOR pathway was again attributed to β-lapachone, promoting the inhibition of EMT transition in NQO1-positive cells.
mTOR↓,
EMT↓,
*BioAv↓, β-lapachone is a promising anticancer drug, its low bioavailability represents a limitation for clinical use due to low solubility in water and gastrointestinal fluids

3729- RF,    Review of the Evidence that Transcranial Electromagnetic Treatment will be a Safe and Effective Therapeutic Against Alzheimer's Disease
- in-vivo, AD, NA
*cognitive↑, demonstrated in multiple studies that daily, long-term electromagnetic field (EMF) treatment in the ultra-high frequency range not only protects Alzheimer’s disease (AD) transgenic mice from cognitive impairment, but also reverses such impairment in
*Aβ↓, daily EMF treatment over months reversed both cognitive impairment (Fig. 2A) and Aβ deposition
*ROS↓, fig 5
*ATP↑,

3733- RF,    Long-term electromagnetic field treatment enhances brain mitochondrial function of both Alzheimer's transgenic mice and normal mice: a mechanism for electromagnetic field-induced cognitive benefit?
- in-vivo, AD, NA
*Aβ↓, ability of EMF treatment to disaggregate Aβ oligomers, which are believed to be the form of Aβ causative to mitochondrial dysfunction in Alzheimer's disease (AD).
*cognitive↑, EMF treatment provides cognitive benefit to both Tg and NT mice
*mt-ROS↓, fig 4
*ATP↑, EMF treatment increases mitochondrial ATP levels selectively in Tg mice

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↓,

3001- RosA,    Therapeutic Potential of Rosmarinic Acid: A Comprehensive Review
- Review, Var, NA
TumCP↓, including in tumor cell proliferation, apoptosis, metastasis, and inflammation
Apoptosis↑,
TumMeta↓,
Inflam↓,
*antiOx↑, RA is therefore considered to be the strongest antioxidant of all hydroxycinnamic acid derivatives
*AntiAge↑, , it also exerts powerful antimicrobial, anti-inflammatory, antioxidant and even antidepressant, anti-aging effects
*ROS↓, RA and its metabolites can directly neutralize reactive oxygen species (ROS) [10] and thereby reduce the formation of oxidative damage products.
BioAv↑, RA is water-soluble, and according to literature data, the efficacy of secretion of this compound in infusions is about 90%
Dose↝, Accordingly, it is possible to consume approximately 110 mg RA daily, i.e., approximately 1.6 mg/kg for adult men weighing 70 kg.
NRF2↑, liver cancer cell line, HepG2, transfected with plasmid containing ARE-luciferin gene, RA predominantly enhances ARE-luciferin activity and promotes nuclear factor E2-related factor-2 (Nrf2) translocation from cytoplasm to the nucleus
P-gp↑, and also increases MRP2 and P-gp efflux activity along with intercellular ATP level
ATP↑,
MMPs↓, RA concurrently induced necrosis and apoptosis and stimulated MMP dysfunction activated PARP-cleavage and caspase-independent apoptosis.
cl‑PARP↓,
Hif1a↓, inhibits transcription factor hypoxia-inducible factor-1α (HIF-1α) expression
GlucoseCon↓, it also suppressed glucose consumption and lactate production in colorectal cells
lactateProd↓,
Warburg↓, may suppress the Warburg effects through an inflammatory pathway involving activator of transcription-3 (STAT3) and signal transducer of interleukin (IL)-6
TNF-α↓, RA supplementation also reduced tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and IL-6 levels, and modulated p65 expression [
COX2↓,
IL6↓,
HDAC2↓, RA induced the cell cycle arrest and apoptosis in prostate cancer cell lines (PCa, PC-3, and DU145) [31]. These effects were mediated through modulation of histone deacetylases expression (HDACs), specifically HDAC2;
GSH↑, RA can also inhibit adhesion, invasion, and migration of Ls 174-T human colon carcinoma cells through enhancing GSH levels and decreasing ROS levels
ROS↓,
ChemoSen↑, RA also enhances chemosensitivity of human resistant gastric carcinoma SGC7901 cells
*BG↓, RA significantly increased insulin index sensitivity and reduced blood glucose, advanced glycation end-products, HbA1c, IL-1β, TNFα, IL-6, p-JNK, P38 mitogen-activated protein kinase (MAPK), and NF-κB levels
*IL1β↓,
*TNF-α↓,
*IL6↓,
*p‑JNK↓,
*p38↓,
*Catalase↑, The reduced activities of CAT, SOD, glutathione S-transferases (GST), and glutathione peroxidase (GPx) and the reduced levels of vitamins C and E, ceruloplasmin, and GSH in plasma of diabetic rats were also significantly recovered by RA application
*SOD↑,
*GSTs↑,
*VitC↑,
*VitE↑,
*GSH↑,
*GutMicro↑, protective effects of RA (30 mg/kg) against hypoglycemia, hyperlipidemia, oxidative stress, and an imbalanced gut microbiota architecture was studied in diabetic rats.
*cardioP↑, Cardioprotective Activity: RA also reduced fasting serum levels of vascular cell adhesion molecule 1 (VCAM-1), inter-cellular adhesion molecule 1 (ICAM-1), plasminogen-activator-inhibitor-1 (PAI-1), and increased GPX and SOD levels
*ROS↓, Finally, in H9c2 cardiac muscle cells, RA inhibited apoptosis by decreasing intracellular ROS generation and recovering mitochondria membrane potential
*MMP↓,
*lipid-P↓, At once, RA suppresses lipid peroxidation (LPO) and ROS generation, whereas in HSC-T6 cells it increases cellular GSH.
*NRF2↑, Additionally, it significantly increases Nrf2 translocation
*hepatoP↑, Hepatoprotective Activity
*neuroP↑, Nephroprotective Activity
*P450↑, RA also reduced CP-produced oxidative stress and amplified cytochrome P450 2E1 (CYP2E1), HO-1, and renal-4-hydroxynonenal expression.
*HO-1↑,
*AntiAge↑, Anti-Aging Activity
*motorD↓, A significantly delays motor neuron dysfunction in paw grip endurance tests,

3037- RosA,    Unraveling rosmarinic acid anticancer mechanisms in oral cancer malignant transformation
- in-vitro, Oral, SCC9 - in-vitro, Oral, HSC3
survivin↓, Rosmarinic acid significantly downregulates BIRC5, the encoded gene for Survivin, in highly invasive oral cancer cells.
AntiCan↑, Rosmarinic acid (RA) has been recognized for its anticancer properties
Vim↓, downregulation of VIM, CADM2, SNAIL1, and SOX9 highlighted the modulation of epithelial-mesenchymal transition
Snail↓,
SOX9↓,
EMT↓,
MMP2↓, remodeling of the extracellular matrix by the downregulation of MMP-2 and MMP-9
MMP9↓,
P-gp↓, RA interacts with P-glycoprotein with the highest docking score of −6.4 kcal/mol.
TumCG↓, RA also shrank the growth and the metabolic activity of multicellular tumor spheroids
ROS↑, RA evokes cell death through the increase of intracellular reactive oxygen species production and the modulation of mitochondrial membrane potential in OSCC cells
MMP↓, significant decrease in the MMP was observed in both cell lines
GSH↓, significant decrease in the glutathione levels in treated HSC-3 cells.
P-gp↓, RA can bind to nine sites of the P-gp ATP model, with a strong binding affinity of −6.3 kcal/mol to −5.4 kcal/mol.
ATP↓,

4898- Sal,    Salinomycin as a potent anticancer stem cell agent: State of the art and future directions
- Review, Var, NA
CSCs↓, Salinomycin, a widely used antibiotic in poultry farming, was identified by the Weinberg group as a potent anti‐CSC agent in 2009.
AntiCan↑, figure 1
ChemoSen↑, potent partner in cotherapies of cancer, as it has been shown to sensitize radiation and many clinically used chemodrugs such as doxorubicin, trastuzumab, gemcitabine, temozolomide, and tamoxifen.
RadioS↑,
Wnt↓, inhibition of Wnt and mitogen‐activated protein kinase (MAPK) pathways,
MAPK↓,
TumAuto↑, the initiation of autophagy, 41 , 42 the decrease of adenosine triphosphate (ATP) levels along with the elevation of reactive oxygen species (ROS) production,
ATP↓,
ROS↑,
DNAdam↑, he triggering of DNA damage and prevention of DNA repair, 32 , 38 , 45 , 46 the induction of endoplasmic reticulum (ER) stress,
ER Stress↑,
CSCsMark↓, suppression of CSC marker expression via the interaction with its cellular binding target nucleolin (NCL).
Iron↑, salinomycin (0.5 μM) treatment led to the accumulation of iron in lysosome,
*toxicity↝, salinomycin‐induced cytotoxic and proinflammatory effects were seen at concentrations ~fivefold higher and ~twofold higher than that relevant to anticancer treatment, whereas the suppression of cell differentiation was observed at a low dose.

4900- Sal,    Anticancer Mechanisms of Salinomycin in Breast Cancer and Its Clinical Applications
- Review, BC, NA
CSCs↓, Salinomycin, a monocarboxylic polyether antibiotic isolated from Streptomyces albus, can precisely kill cancer stem cells (CSCs), particularly BCSCs, by various mechanisms, including apoptosis, autophagy, and necrosis.
Apoptosis↑,
TumAuto↑,
necrosis↑,
TumCP↓, salinomycin can inhibit cell proliferation, invasion, and migration in BC and reverse the immune-inhibitory microenvironment to prevent tumor growth and metastasis.
TumCI↓,
TumCMig↓,
TumCG↓,
TumMeta↓,
eff↑, Salinomycin is over 100 times more effective against BCSCs than paclitaxel, the traditional chemotherapy drug for the treatment of BC
Bcl-2↓, downregulation of Bcl-2 expression, and decreases their migration capacity, which is accompanied by downregulation of c-Myc and Snail expression
cMyc↓,
Snail↓,
ALDH↓, salinomycin reduces aldehyde dehydrogenase activity and the expression of MYC, AR, and ERG; it induces oxidative stress and inhibits nuclear factor (NF)-κB activity
Myc↓,
AR↓,
ROS↑, Salinomycin also induces autophagy by increasing intracellular ROS level, which is accompanied by MAPK signaling pathway activation
NF-kB↓,
PTCH1↓, significantly reduces tumor growth, which is accompanied by decreased PTCH, SMO, Gli1, and Gli2 expression
Smo↓,
Gli1↓,
GLI2↓,
Wnt↓, Figure 2
mTOR↓,
GSK‐3β↓,
cycD1/CCND1↓,
survivin↓,
P21↑,
p27↑,
CHOP↑,
Ca+2↑, cytosolic
DNAdam↑,
Hif1a↓,
VEGF↓,
angioG↓,
MMP↓, salinomycin can affect the cell membrane potential and reduce the level of ATP to induce mitophagy and mitoptosis.
ATP↓,
p‑P53↑, Salinomycin increases DNA breaks in BC cells as well as the expression of phosphorylated p53 and γH2AX in Hs578T cells.
γH2AX↑,
ChemoSen↑, Table 3 Synergistic anticancer co-action of salinomycin with other agents in BC.

4903- Sal,    Salinomycin: A new paradigm in cancer therapy
- Review, Var, NA
TumCG↓, multiple pathways by which salinomycin inhibits tumor growth
ATP↓, Salinomycin decreases the expression of adenosine triphosphate–binding cassette transporter in multidrug resistance cells
CSCs↓, Salinomycin selectively targets cancer stem cells.
ROS↑, inhibited growth and migration of prostate cancer cells,37 and led to reactive oxygen species (ROS) accumulation in androgen-dependent and independent prostate cancer cells.
Casp↑, via caspase activation and destabilization of mitochondrial membrane potential
MMP↓,
selectivity↑, Salinomycin also acted on OVCAR-3 human ovarian cancer cells through caspase-mediated apoptosis without harming normal cells
OXPHOS↓, Salinomycin inhibited mitochondrial oxidative phosphorylation without affecting the substrate-level phosphorylation.
STAT3↓, CSC population was inhibited by STAT3 down-regulation
P53↑, Salinomycin increased tumor-suppressor protein p53 and DNA damaging protein pH2AX and decreased cyclin D1 level, which led to cell-cycle arrest and high DNA damage.
γH2AX↑,
cycD1/CCND1↓,
TumCCA↑,
DNAdam↑,
ChemoSen↑, Salinomycin works synergistically with conventional chemotherapeutic drugs to inhibit invasion and migration of cancer cells.

4909- Sal,    Salinomycin: Anti-tumor activity in a pre-clinical colorectal cancer model
- vitro+vivo, CRC, NA
AntiTum↑, salinomycin alone or in combination with FOLFOX exerts superior antitumor activity compared to FOLFOX therapy in a patient-derived mouse xenograft model of colorectal cancer
Apoptosis↑, Salinomycin induces apoptosis of human colorectal cancer cells, accompanied by accumulation of dysfunctional mitochondria and reactive oxygen species
mtDam↑,
ROS↑, Accumulation of dysfunctional mitochondria and increased production of reactive oxygen species upon salinomycin treatment
SOD1↓, These effects are associated with expressional down-regulation of superoxide dismutase-1 (SOD1) in response to salinomycin treatment.
ChemoSen↑, salinomycin alone or in combination with 5-fluorouracil and oxaliplatin exerts increased antitumoral activity compared to common chemotherapy.
CSCs↑, Anti-stem cell activity of salinomycin in TIC cultures
ALDH↓, Strikingly, exposure to 5-FU and oxaliplatin resulted in a more pronounced reduction of the ALDH1+ population compared to salinomycin treatment
TumCG↓, Salinomycin inhibits tumor growth in a patient-derived xenograft model
TumCP↓, Salinomycin inhibits proliferation, induces cell death and abolishes ATP production of human colorectal cancer cells
TumCD↑,
ATP↓,

5125- Sal,    Salinomycin induced ROS results in abortive autophagy and leads to regulated necrosis in glioblastoma
- in-vitro, GBM, NA
ER Stress↑, SLM induces a potent endoplasmic reticulum (ER) stress followed by the trigger of the unfolded protein response (UPR) and an aberrant autophagic flux that culminated in necrosis due to mitochondria and lysosomal alterations.
UPR↑,
autoF↓, SLM treatment does not trigger apoptosis and blocks the autophagy flux in glioma cell line
lysosome↝,
ROS↑, aberrant autophagic flux was orchestrated by the production of Reactive Oxygen Species (ROS)
lipid-P↑, our data suggest that in our system the oxidative stress blocks the autophagic flux through lipid oxidation.
CSCs↓, SLM induces a potent antitumor effect in brain tumor stem cells (BTSCs) and established adult and pediatric glioma cell lines in vitro
necrosis↑, SLM induces necrosis cell death
ATP↓, with increasing doses of SLM displayed a decrease in intracellular ATP levels
MMP↓, SLM treated cells displayed significantly lower ΔΨm than untreated cells
MOMP↑, SLM induces mitochondrial MOMP.
DNAdam↑, We observed double strand breaks in SLM-treated cells (Figure 4C) and it is possible that this DNA damage is induced as a consequence of AIF internalization.
AIF↑,
lysoMP↑, hypothesis that SLM treatment triggers an autophagic process that cannot proceed adequately because of LMP resulting from oxidative stress.
MitoP↑, In addition, impairment of mitochondrial activity would trigger mitophagy, with engulfment of the organelle and initiation of autophagy.
Ca+2↑, The elevated levels of calcium and ROS inside mitochondria results in MOMP

1403- SDT,  BBR,    From 2D to 3D In Vitro World: Sonodynamically-Induced Prooxidant Proapoptotic Effects of C60-Berberine Nanocomplex on Cancer Cells
- in-vitro, Cerv, HeLa - in-vitro, Lung, LLC1
eff↑, revealed that US irradiation alone had negligible effects on LLC and HeLa cancer cells. However, both monolayers and spheroids irradiated with US in the presence of the C60-Ber exhibited a significant decrease in viability
tumCV↓,
ATP↓,
ROS↑,
Casp3↑,
Casp7↑,
mtDam↑,

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↓,

2445- SFN,    Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, SkBr3
TumCCA↑, SFN (5-10 µM) promoted cell cycle arrest, elevation in the levels of p21 and p27 and cellular senescence
P21↑,
p27↑,
NO↑, effects were accompanied by nitro-oxidative stress, genotoxicity and diminished AKT signaling
Akt↓,
ATP↓, decreased pools of ATP and AMPK activation, and autophagy induction
AMPK↑,
TumAuto↑,
DNMT1↓, decreased levels of DNA methyltransferases (DNMT1, DNMT3B)
HK2↓, A decrease in HK2 levels was observed in SFN-treated MDA-MB-231 cells
PKM2↓, and a decrease in PKM2 levels was noticed in SFN-treated MDA-MB-231 and SK-BR-3 cells
HDAC3↓, . In contrast, HDAC3 , HDAC4 , HDAC6 , HDAC7 , HDAC8 ), HDAC9 and HDAC10 (histone deacetylase 10) mRNA levels were decreased in SFN-treated MDA-MB-231 cells
HDAC4↓,
HDAC8↓,

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

3298- SIL,    Silibinin, a natural flavonoid, induces autophagy via ROS-dependent mitochondrial dysfunction and loss of ATP involving BNIP3 in human MCF7 breast cancer cells
- in-vitro, BC, MCF-7
LC3II↑, silibinin triggered the conversion of light chain 3 (LC3)-I to LC3-II, promoted the upregulation of Atg12-Atg5 formation, increased Beclin-1 expression, and decreased the Bcl-2 level.
Beclin-1↑,
Bcl-2↓,
ROS↑, Moreover, we noted elevated reactive oxygen species (ROS) generation, concomitant with the dissipation of mitochondrial transmembrane potential (ΔΨm) and a drastic decline in ATP levels following silibinin treatment,
MMP↓,
ATP↓,
eff↓, which were effectively prevented by the antioxidants, N-acetylcysteine and ascorbic acid
BNIP3?, silibinin upregulated BNIP3 protein and transcript levels
TumAuto↑, uggesting that the MCF7 cells were more sensitive to silibinin-induced autophagic cell death under the starvation condition.
eff↑, more sensitive to silibinin-induced autophagic cell death under the starvation condition.

3282- SIL,    Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions
- Review, NA, NA
hepatoP↑, This group of flavonoids has been extensively studied and they have been used as hepato-protective substances
AntiCan↑, however, silymarin compounds have clear anticancer effects
TumCMig↓, decreasing migration through multiple targeting, decreasing hypoxia inducible factor-1α expression, i
Hif1a↓, In prostate cancer cells silibinin inhibited HIF-1α translation
selectivity↑, antitumoral activity of silymarin compounds is limited to malignant cells while the nonmalignant cells seem not to be affected
toxicity∅, long history of silymarin use in human diseases without toxicity after prolonged administration.
*antiOx↑, as an antioxidant, by scavenging prooxidant free radicals
*Inflam↓, antiinflammatory effects similar to those of indomethacin,
TumCCA↑, MDA-MB 486 breast cancer cells, G1 arrest was found due to increased p21 and decreased CDKs activity
P21↑,
CDK4↓,
NF-kB↓, human prostate carcinoma cells, silymarin decreased ligand binding to Erb1 135 and NF-kB expression was strongly inhibited by silymarin in hepatoma cell
ERK↓, human prostate carcinoma cells, silymarin decreased ligand binding to Erb1 135 and NF-kB expression was strongly inhibited by silymarin in hepatoma cell
PSA↓, Treating prostate carcinoma cells with silymarin the levels of PSA were significantly decreased and cell growth was inhibited through decreased CDK activity and induction of Cip1/p21 and Kip1/p27. 1
TumCG↓,
p27↑,
COX2↓, such as anti-COX2 and anti-IL-1α activity, 140 antiangiogenic effects through inhibition of VEGF secretion, upregulation of Insulin like Growth Factor Binding Protein 3 (IGFBP3), 141 and inhibition of androgen receptors.
IL1↓,
VEGF↓,
IGFBP3↑,
AR↓,
STAT3↓, downregulation of the STAT3 pathway which was seen in many cell models.
Telomerase↓, silymarin has the ability to decrease telomerase activity in prostate cancer cells
Cyt‑c↑, mitochondrial cytochrome C release-caspase activation.
Casp↑,
eff↝, Malignant p53 negative cells show only minimal apoptosis when treated with silymarin. Therefore, one conclusion is that silymarin may be useful in tumors with conserved p53.
HDAC↓, inhibit histone deacetylase activity;
HATs↑, increase histone acetyltransferase activity
Zeb1↓, reduce expression of the transcription factor ZEB1
E-cadherin↑, increase expression of E-cadherin;
miR-203↑, increase expression of miR-203
NHE1↓, reduce activation of sodium hydrogen isoform 1 exchanger (NHE1)
MMP2↓, target β catenin and reduce the levels of MMP2 and MMP9
MMP9↓,
PGE2↓, reduce activation of prostaglandin E2
Vim↓, suppress vimentin expression
Wnt↓, inhibit Wnt signaling
angioG↓, Silymarin inhibits angiogenesis.
VEGF↓, VEGF downregulation
*TIMP1↓, Silymarin has the capacity to decrease TIMP1 expression166–168 in mice.
EMT↓, found that silibinin had no effect on EMT. However, the opposite was found in other malignant tissues160–162 where it showed inhibitory effects.
TGF-β↓, Silibinin reduces the expression of TGF β2 in different tumors such as triple negative breast, 174 prostate, and colorectal cancers.
CD44↓, Silibinin decreased CD44 expression and the activation of EGFR (epidermal growth factor receptor)
EGFR↓,
PDGF↓, silibinin had the ability to downregulate PDFG in fibroblasts, thus decreasing proliferation.
*IL8↓, Flavonoids, in general, reduce levels of IL-8. Curcumin, 200 apigenin, 201 and silybin showed the ability to decrease IL-8 levels
SREBP1↓, Silymarin inhibited STAT3 phosphorylation and decreased the expression of intranuclear sterol regulatory element binding protein 1 (SREBP1), decreasing lipid synthesis.
MMP↓, reduced membrane potential and ATP content
ATP↓,
uPA↓, silibinin decreased MMP2, MMP9, and urokinase plasminogen activator receptor level (uPAR) in neuroblastoma cells. uPAR is also a marker of cell invasion.
PD-L1↓, Silibinin inhibits PD-L1 by impeding STAT5 binding in NSCLC.
NOTCH↓, Silybin inhibited Notch signaling in hepatocellular carcinoma cells showing antitumoral effects
*SIRT1↑, Silymarin can also increase SIRT1 expression in other tissues, such as hippocampus, 221 articular chondrocytes, 222 and heart muscle
SIRT1↓, Silymarin seems to act differently in tumors: in lung cancer cells SIRT downregulated SIRT1 and exerted multiple antitumor effects such as reduced adhesion and migration and increased apoptosis.
CA↓, Silymarin has the ability to inhibit CA isoforms CA I and CA II.
Ca+2↑, ilymarin increases mitochondrial release of Ca++ and lowers mitochondrial membrane potential in cancer cell
chemoP↑, Silymarin: Decreasing Side Effects and Toxicity of Chemotherapeutic Drugs
cardioP↑, There is also evidence that it protects the heart from doxorubicin toxicity, however, it is less potent than quercetin in this effect.
Dose↝, oral administration of 240 mg of silybin to 6 healthy volunteers the following results were obtained 377 : maximum\,plasmaconcentration0.34±0.16⁢𝜇⁢g/m⁢L
Half-Life↝, and time to maximum plasma concentration 1.32 ± 0.45 h. Absorption half life 0.17 ± 0.09 h, elimination half life 6.32 ± 3.94 h
BioAv↓, silymarin is not soluble in water and oral administration shows poor absorption in the alimentary tract (approximately 1% in rats,
BioAv↓, Our conclusion is that, from a bioavailability standpoint, it is much easier to achieve migration inhibition, than proliferative reduction.
BioAv↓, Combination with succinate: is available on the market under the trade mark Legalon® (bis hemisuccinate silybin). Combination with phosphatidylcholine:
toxicity↝, 13 g daily per os divided into 3 doses was well tolerated. The most frequent adverse event was asymptomatic liver toxicity.
Half-Life↓, It may be necessary to administer 800 mg 4 times a day because the half-life is short.
ROS↓, its ability as an antioxidant reduces ROS production
FAK↓, Silibinin decreased human osteosarcoma cell invasion through Erk inhibition of a FAK/ERK/uPA/MMP2 pathway

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

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

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↓,

2360- SK,    Shikonin inhibits growth, invasion and glycolysis of nasopharyngeal carcinoma cells through inactivating the phosphatidylinositol 3 kinase/AKT signal pathway
- in-vitro, NPC, HONE1 - in-vitro, NPC, SUNE-1
TumCP↓, Shikonin treatment effectively suppressed cell proliferation and induced obvious cell apoptosis compared with the control.
Apoptosis↑,
TumCMig↓, Shikonin treatment suppressed cell migration and invasion effectively.
TumCI↓,
GlucoseCon↓, Shikonin treatment suppressed cell glucose uptake, lactate release and ATP level.
lactateProd↓,
ATP↓,
PKM2↓, activity of PKM2 was also largely inhibited by Shikonin
PI3K↓, PI3K/AKT signal pathway was inactivated by Shikonin treatment
Akt↓,
MMP3↓, MMP-3 and MMP-9 was decreased and the expression of TIMP was increased by Shikonin in HONE1 and SUNE-1 cells
MMP9↓,
TIMP1↑,

2190- SK,    Shikonin exerts antitumor activity by causing mitochondrial dysfunction in hepatocellular carcinoma through PKM2-AMPK-PGC1α signaling pathway
- in-vitro, HCC, HCCLM3
TumCP↓, shikonin inhibited the proliferation, migration, and invasiveness of HCCLM3 cells, and promoted cell apoptosis in a dose-dependent manner
TumCMig↓,
TumCI↓,
Apoptosis↑,
MMP↓, shikonin affected mitochondrial function by disrupting mitochondrial membrane potential and oxidative stress (OS) status.
ROS↑,
OCR↓, shikonin decreased the oxygen consumption rate of HCCLM3 cells, as well as the levels of ATP and metabolites involved in the tricarboxylic acid cycle (TCA cycle)
ATP↓,
PKM2↓, Shikonin decreased the expression of PKM2 in the mitochondria

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↑,

1284- SK,    Shikonin induces ferroptosis in multiple myeloma via GOT1-mediated ferritinophagy
- in-vitro, Melanoma, RPMI-8226 - in-vitro, Melanoma, U266
Ferroptosis↑, SHK treatment leads to the ferroptosis of MM cells
LDH↓,
ROS↑, Cellular mitochondrial lipid ROS also increased after SHK treatment
Iron↑,
lipid-P↑,
ATP↓, extracellular release of Adenosine 5’-triphosphate (ATP) and High mobility group protein B1 (HMGB1
HMGB1↓,
GPx4↓, Additionally, the ferroptosis markers GPX4 and solute carrier family 7 member 11 (xCT/SLC7A11) were downregulated at both the transcriptional and translational levels after SHK treatment
MDA↑, SHK treatment led to an increase in MDA content in cells. In contrast, the levels of SOD and GSH decreased in cells
SOD↓,
GSH↓,

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.

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,

2411- UA,    Ursolic acid in health and disease
- Review, Var, NA
Inflam↓, UA because of its beneficial effects, which include anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-carcinogenic effects
antiOx↑,
NF-kB↓, Colon cancer HCT116, HT29 20 μM for 8 hour ↓ NF-kB, Bcl-xL, Bcl-2, and cyclin D1
Bcl-xL↓,
Bcl-2↓,
cycD1/CCND1↓,
Ki-67↓, ↓ Ki67, CD31, STAT3, and EGFR, ↑ p53 and p21 mRNA expression
CD31↓,
STAT3↓,
EGFR↓,
P53↑,
P21↓,
HK2↓, MCF-7, MDA-MB-231 20 μM for 24 hours ↓ HK2, PKM2, ATP, and lactate ↓ pERK1/2, and depolarization of mitochondrial membrane potential, ↑ Nitric oxide and ATM
PKM2↓,
ATP↓,
lactateProd↓,
p‑ERK↓,
MMP↓,
NO↑,
ATM↑,
Casp3↑, T24 cancer cells ↑ Caspase 3 activity ↑ AMPK activation ↑ JNK activation
AMPK↑,
JNK↑,
FAO↑, 80 μM UA reduces triglyceride (TG) and cholesterol levels by increasing fatty acid oxidation and decreasing fatty acid synthesis in hepatocytes
FASN↓,
*GSH↑, ↑ Vitamin C, E, GSH, SOD, CAT, GPx, GST, and GR in heart
*SOD↑,
*Catalase↑,
*GPx↑,
*GSTs↑,
neuroP↑, This demonstrates that UA has a protective effect against various inflammatory conditions of the brain.

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.

4869- Uro,    Urolithin A in Central Nervous System Disorders: Therapeutic Applications and Challenges
- Review, AD, NA - Review, Park, NA - Review, Stroke, NA
*MitoP↑, key biological effects of UA, including its promotion of mitophagy and mitochondrial homeostasis, as well as its anti-inflammatory, antioxidant, anti-senescence, and anti-apoptotic properties
*Inflam↓,
*antiOx↑,
*Risk↓, UA’s therapeutic potential in CNS disorders, such as Alzheimer’s disease, Parkinson’s disease, and stroke.
*Aβ↓, UA enhances microglial phagocytosis of Aβ plaques, suppresses neuroinflammation, and reduces tau hyperphosphorylation by restoring mitophagy to eliminate abnormal mitochondria
*p‑tau↓,
*p62↓, In doxorubicin-induced cardiomyopathy mice, UA upregulates p62, LC3-II, PINK1, and Parkin expression, restoring impaired mitophagy, mitigating membrane potential loss and ROS accumulation,
*PARK2↑,
*MMP↑,
*ROS↓,
*Strength↑, Randomized controlled trials in healthy middle-aged and older adults show that oral supplementation with 500–1000 mg of UA significantly improves skeletal muscle endurance and mitochondrial efficiency, reduces plasma inflammatory markers (such as C-r
*CRP↓,
*IL1β↓, UA activates sirtuin 1 (SIRT1)-mediated deacetylation of NF-κB p65, suppressing glial cell activation and the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α)
*IL6↓,
*TNF-α↓,
*AMPK↑, UA enhances brain adenosine 5′-monophosphate-activated protein kinase (AMPK) activation, attenuating NF-κB and MAPK activity, mitigating neuroinflammation, and supporting synaptic recovery
*NF-kB↓,
*MAPK↓,
*p62↑, In a renal ischemia-reperfusion injury model, UA activates the p62—kelch-like ECH-associated protein 1 (Keap1)—nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, boosting superoxide dismutase and catalase activity while lowering ROS levels
*NRF2↑,
*SOD↑,
*Catalase↑,
*HO-1↑, UA upregulates the Keap1-Nrf2/heme oxygenase 1 (HO-1) pathway to inhibit ferroptosis and reduce lipid peroxide accumulation in lung tissue
*Ferroptosis↓,
*lipid-P↓,
*Cartilage↑, reducing cartilage degradation and synovial inflammation
*PI3K↓, UA suppresses the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and Akt/IκB kinase (IKK)/NF-κB signaling pathways, reducing neuronal apoptosis while enhancing BBB integrity and neurological outcomes
*Akt↓,
*mTOR↓,
*Apoptosis↓,
*neuroP↑,
*Bcl-2↓, cerebral artery occlusion model, UA treatment lowers Bcl-2 expression and elevates Bcl-2 associated X protein (Bax) and caspase-3 levels
*BAX↑,
*Casp3↑,
*ATP↑, UA restores mitochondrial membrane potential and ATP production in cardiomyocytes, balancing carnitine palmitoyltransferase1-dependent fatty acid oxidation to reduce apoptosis
*eff↑, in humanized homozygous amyloid beta knockin mice modeling late-onset AD, UA combined with green tea extract (Epigallocatechin gallate) more effectively reduces brain Aβ40 and Aβ42 levels compared to UA alone [106].
*motorD↑, UA administration elevated striatal dopamine levels and enhanced motor coordination, accompanied by suppression of NLRP3 inflammasome activation
*NLRP3↓,
*radioP↑, In a radiation-induced primary astrocyte model, UA activated the PINK1/Parkin-mediated mitophagy pathway, significantly reducing ROS levels in both cells and mitochondria,
*BBB↑, preclinical studies showing that UA primarily crosses the mouse BBB

4871- Uro,  DHA,  LT,    A Synergistic Combination of DHA, Luteolin, and Urolithin A Against Alzheimer’s Disease
- in-vitro, AD, NA
*ATP↑, significantly higher relative ATP levels
*Apoptosis↓, These results together indicated that pre-treatment with the three-compound combination, D5L5U5 attenuated Aβ1–42-induced toxicity very effectively.

4874- Uro,  EGCG,    A Combination Therapy of Urolithin A+EGCG Has Stronger Protective Effects than Single Drug Urolithin A in a Humanized Amyloid Beta Knockin Mice for Late-Onset Alzheimer's Disease
- in-vivo, AD, NA
*motorD↑, increased positive effects of urolithin A and a combination treatment of urolithin A+EGCG in hAbKI mice for phenotypic behavioral changes including motor coordination, locomotion/exploratory activity, spatial learning and working memory
*memory↑,
*MitoP↑, mitophagy and autophagy genes were upregulated
*Aβ↓, The levels of amyloid beta (Aβ) 40 and Aβ42 are reduced in both treatments, however, the reduction is higher for combined treatment
*mitResp↑, Mitochondrial respiration is stronger for urolithin A compared to EGCG, indicating that mitophagy enhancer, urolithin A is a better and more promising molecule to enhance mitophagy activity.
*Nrf1↑, table4
*PINK1↑,
*PARK2↑,
*ATG5↑,
*Bcl-2↑,
*H2O2↓, we found hydrogen peroxide levels were reduced in urolithin A (p = 0.0008) and urolithin A+EGCG (p = 0.0004) treated hAbKI mice relative to untreated mice.
*ROS↓, urolithin A and EGCG act as free radical scavengers in hAbKI mice
*lipid-P↓, (lipid peroxidation) were also significantly reduced in urolithin A (p = 0.0003) and urolithin A+EGCG (p = 0.0002) treated hAbKI mice relative to untreated hAbKI mice
*mt-ATP↑, mitochondrial ATP levels were increased in urolithin A (p = 0.007) and urolithin A+EGCG (p = 0.0002) treated hAbKI mice relative to hAbKI untreated mice.

4314- VitB1/Thiamine,    Unraveling the molecular mechanisms of vitamin deficiency in Alzheimer's disease pathophysiology
- Review, AD, NA
*Risk↓, Its deficiency disrupts glucose metabolism, impairs neurotransmitter production and DNA synthesis, and increases the risk of AD and neurological deficits
*GlucoseCon↑,
*cognitive↑, Thiamine supplementation, especially benfotiamine, has been shown to improve cognitive function in mild AD, while higher dietary intake supports cognitive impairments
*ATP↑, Low thiamine impairs glucose metabolism, reducing ATP production and increasing ROS, leading to mitochondrial and synaptic dysfunction, key features of AD.
*ROS↓,
*NADPH↑, Thiamine aids in producing ribose-5-phosphate and NADPH, essential for nucleotide synthesis.
*Aβ↓, Low thiamine reduces antioxidant capacity, leading to ROS accumulation and oxidative damage to proteins, lipids, and DNA. This triggers neurodegeneration processes, including development of Aβ plaques
*APP↓, The increase in APP activates beta-site APP cleaving enzymes-1 (BACE1), promoting its cleavage and enhancing the secretion of the Aβ monomers.
*BACE↓,

4037- VitB12,  FA,    Mechanistic Link between Vitamin B12 and Alzheimer’s Disease
- Review, AD, NA
*antiOx↑, antioxidant properties of vitamin B12 are discussed to be accomplished by different mechanisms, including direct scavenging of ROS, particularly superoxide in the cytosol and mitochondria
*ROS↓,
*GSH↑, indirectly stimulating ROS scavenging by preservation of glutathione [
*Inflam↓, vitamin B12 might protect against inflammation-induced oxidative stress by modulating cytokine and growth factor production, including interleukin-6, tumour necrosis factor alpha (TNF-α) and epidermal growth factor.
*IL6↓,
*TNF-α↓,
*other↑, Vitamin B12 is an important cofactor of methionine-synthase, converting homocysteine into methionine.
*other↑, A folate and/or vitamin B12 deficiency with a reduction in genomic and non-genomic methylation processes caused by folate and/or vitamin B12 deficiency, might lead to decreased DNA stability
*other↑, methionine metabolism strongly depends on three important cofactors, namely, folate (vitamin B9), vitamin B6 and vitamin B12.
*Aβ↓, elevation of Aβ deposits in the hippocampus and cortex of an AD mouse model fed with a folate/vitamin B6/vitamin B12-deficient diet.
*memory↑, The simultaneous supplementation of folate and vitamin B12 attenuated the hyperhomocysteinemic-induced changes in APP processing and improved memory in these rats.
*p‑tau↓, Supplementation of folate and vitamin B12 also revealed positive effects on Aβ level and tau hyperphosphorylation in the retina of hyperhomocysteinemic three- to four-month-old rats
*APP↓, Notably, this increase in the APP, PS1 and BACE1 protein levels could be reverted by folate/vitamin B12 supplementation.
*BACE↓,
*ATP↑, C. elegans receiving a vitamin B12-containing diet showed a higher ATP level, decreased mitochondrial fragmentation and reduced oxidative species (ROS) than those without vitamin B12.
*neuroP↑, Significant neuroprotective effects of vitamin B12 were already apparent at 2 µM vitamin B12

4315- VitB2,    Unraveling the molecular mechanisms of vitamin deficiency in Alzheimer's disease pathophysiology
*GlucoseCon↑, Riboflavin (vitamin B2) is essential for the metabolism of carbohydrates, fats, and proteins into glucose for energy
*ATP↑, It acts as a precursor to flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), essential for ATP production.
*homoC↓, Studies show that riboflavin regulates homocysteine metabolism, and its deficiency may elevate homocysteine levels, which increase the AD
*ROS↓, Riboflavin deficiency disrupts this pathway, reducing FMN and FAD levels, impairing mitochondrial function, and increasing ROS and oxidative stress. ROS buildup can harm neurons and contributes to Aβ plaques and neurofibrillary tangles, key features
*Aβ↓, Riboflavin regulates homocysteine metabolism, preventing excess Aβ formation.
*Aβ↓,
*Inflam↓, The ensuing neuroinflammation makes amyloid pathology worse, starting a vicious cycle that quickens the onset of AD

4317- VitB5,    Unraveling the molecular mechanisms of vitamin deficiency in Alzheimer's disease pathophysiology
- Review, AD, NA
*Ach↑, It synthesizes key biomolecules, including haemoglobin, acetylcholine, and cholesterol synthesis for cell membrane integrity.
*ROS↓, Its deficiency disrupts the TCA cycle, and promotes oxidative stress, neuroinflammation, tau hyperphosphorylation, and Aβ plaque formation, key attributes of AD.
*Inflam↓,
*p‑tau↓,
*Aβ↓,
*Acetyl-CoA↑, Its deficiency prevents the production of CoA, which reduces the levels of acetyl-CoA, impairing neurotransmitter synthesis, ATP production, and tricarboxylic acid cycle function, thereby disrupting neuronal survival and function
*ATP↑,
*ChAT↑, Vitamin B5 deficiency impairs acetylcholine biosynthesis by inhibiting choline acetyltransferase (ChAT), which catalyzes acetyl-CoA and choline conversion
*memory↑, Acetylcholine decline impairs memory, and vitamin B5 deficiency disrupts pathways dependent on CoA-derived acyl groups, impairing fatty acid synthesis and causing neuronal dysfunction

4330- VitB5,    Metabolic changes and inflammation in cultured astrocytes from the 5xFAD mouse model of Alzheimer’s disease: Alleviation by pantethine
- in-vivo, AD, NA
*neuroP↑, Pantethine, the vitamin B5 precursor, known to be neuroprotective and anti-inflammatory, alleviated the pathological pattern in Tg astrocytes
*Inflam↓, pantethine has anti-inflammatory properties,
*ATP↑, Importantly, ATP had its levels increased by 44% in pantethine-treated Tg astrocytes compared to untreated.
*G6PD↑, Pantethine treatment increased both G6PD and PK activity in WT by about 40% and 25%, respectively.
*NADPH↑, in agreement, astrocyte NADPH levels paralleled the changes of G6PD activity described above
*IL1β↓, Pantethine treatment significantly reduced both IL-1β mRNA and protein expression in all conditions where it was applied
*other↝, Administered, at the right time during the disease progression, the pleiotropic action of this natural compound could therefore bring improvement in a complex pathological situation such as AD.

1067- VitC,    Vitamin C activates pyruvate dehydrogenase (PDH) targeting the mitochondrial tricarboxylic acid (TCA) cycle in hypoxic KRAS mutant colon cancer
- in-vivo, CRC, NA
PDK1↓,
Hif1a↓,
GLUT1↓,
ATP↓, Vitamin C induced remarkable ATP depletion
MMP↓,

627- VitC,    High-Dose Vitamin C for Cancer Therapy
- Review, NA, NA
ROS↑,
PARP↑, ROS activates poly (ADP-ribose) polymerase (PARP), which depletes NAD+
GAPDH↓, Hindering GAPDH can result in an “energy crisis”, due to the decrease in ATP production
DNAdam↑,
ATP↓,

633- VitC,    Diverse antitumor effects of ascorbic acid on cancer cells and the tumor microenvironment
- Analysis, NA, NA
Fenton↑,
ROS↑,
EMT↓, Ascorbic acid is also known to inhibit EMT of tumor cells
DNAdam↑,
PARP↑, DNA damage increases PARP activity, thereby decreasing NAD+ levels
NAD↓, NAD+
ATP↓,
Apoptosis↑,

631- VitC,    Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2
- vitro+vivo, Liver, NA
SVCT-2∅, response to VC was correlated with sodium-dependent vitamin C transporter 2 (SVCT-2) expressions. Most importantly, SVCT-2 was highly expressed in liver CSCs
ROS↑,
DNAdam↑,
ATP↓,
TumCCA↑,
Apoptosis↑,
OS↑, VC use was linked to improved disease-free survival (DFS) in HCC patients
CD133↓, CD133+
EpCAM↓, EpCAM+
OV6↓, OV6+
γH2AX↑, p-H2AX induced by VC

630- VitC,    Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress
- in-vitro, BC, MCF-7 - in-vitro, BC, HT-29
TCA↑,
ATP↓,
NAD↓, vitamin C caused cell death through NAD depletion in MCF7 and HT29 cells
H2O2↑,
GSH/GSSG↓,

623- VitC,    The Involvement of Ascorbic Acid in Cancer Treatment
- Review, NA, NA
ROS↑,
GLUT1↓, VC may impede glucose transport and adenosine triphosphate (ATP) production
ATP↓,

3138- VitC,    The Hypoxia-inducible Factor Renders Cancer Cells More Sensitive to Vitamin C-induced Toxicity
- in-vitro, RCC, RCC4 - in-vitro, CRC, HCT116 - in-vitro, BC, MDA-MB-435 - in-vitro, Ovarian, SKOV3 - in-vitro, Colon, SW48 - in-vitro, GBM, U251
eff↑, Here, we show that a Warburg effect triggered by activation of the hypoxia-inducible factor (HIF) pathway greatly enhances Vc-induced toxicity in multiple cancer cell lines
Warburg↓,
BioAv↑, HIF increases the intracellular uptake of oxidized Vc through its transcriptional target glucose transporter 1 (GLUT1),
ROS↑, resulting high levels of intracellular Vc induce oxidative stress and massive DNA damage, which then causes metabolic exhaustion by depleting cellular ATP reserves.
DNAdam↑,
ATP↓,
eff↑, Activation of HIF increases the susceptibility to Vc-induced cell toxicity
necrosis↑, High intracellular levels of Vc increase ROS and trigger necrosis in VHL-defective renal cancer cells.
PARP↑, Activation of the PARP Pathway by Vc Depletes Intracellular ATP Reserves in VHL-defective Renal Cancer Cells

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↓,

4090- VitK2,  ProBio,    Vitamin K2 Holds Promise for Alzheimer's Prevention and Treatment
- Review, AD, NA
*antiOx↑, figure 1
*Inflam↓,
*Aβ↓,
*memory↑, positive association between high serum levels of VK1 and verbal episodic memory,
*NF-kB↓, suppressing the NF-κB pathway
*ROS↓, reduced the presence of reactive oxygen species (ROS), and increased the amount of glutathione, a powerful anti-oxidant.
*GSH↑,
*ATP↑, increased ATP production in pink1 mutants
*p‑tau↓, a 2020 study found that VK2 mitigated tau phosphorylation and cognitive deficits induced by sevoflurane in newborn mic
*cardioP↑, In a study that followed 4807 men and women of age 55 and above for more than seven years, the participants in the highest tercile for VK2 intake had a 41% lower risk of CVD when compared with the those in the lowest tercile
*other↝, one study suggests that the amount of VK2 synthesized in the gut by far exceeds human nutritional requirements, even if only a small fraction is absorbed [138].
*cognitive↑, 60 AD patients who received a probiotic containing a mix of the bacteria Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum for 12 weeks reached a similar conclusion

1818- VitK2,    New insights on vitamin K biology with relevance to cancer
- Review, Var, NA
TumCG↓, A few small randomized trials support the concept that vitamin K supplementation can retard cancer development and/or progression
ChemoSen↑, phase 2 randomized placebo-controlled trial in HCC patients demonstrated that MK4 supplementation (45 mg/day orally) enhanced the efficacy of the multi-kinase inhibitor sorafenib
toxicity∅, long term vitamin K supplementation is safe and may offer survival benefit in HCC patients.
OS↑,
BMD↑, Primary Outcomes: Bone density
eff↑, In studies where both forms of the vitamin have been compared, MKs generally exerted more potent anticancer effects than PK.
MMP↓, direct effects on mitochondrial membrane depolarization and reactive oxygen species (ROS)
ROS↑,
eff↓, ROS neutralization by antioxidants (N-acetyl cysteine (NAC) and alpha-tocopherol) or BAK knockdown prevented MK4 mediated mitochondrial disruption and apoptosis
ERK↑, activates ERK, JNK/p38 MAPK
JNK↑,
p38↑,
Cyt‑c↑, cytochrome c release
Casp↑, caspase activation
ATP↓, reducing ATP production and increasing lactate production
lactateProd↑,
AMPK↑, which activates AMPK
Rho↓, via inhibition of RhoA
TumCG↓, mouse xenograft studies, treatment with MK4 administered in water at a calculated dose of 20 mg/kg/d significantly reduced growth of established HCCs
BioAv↑, Phylloquinone (K1) is the major dietary form, but it is converted into menaquinone (K2) in tissues.
cardioP↑, optimal vitamin K status is common in adults and may contribute to chronic diseases such as osteoporosis, type 2 diabetes and cardiovascular disease.
Risk↓, Observational studies suggest that low vitamin K intake increases cancer risk(more lowers risk)

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: 165

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ATF3↓, 1,   Catalase↓, 1,   Catalase↑, 1,   compI↓, 1,   CYP1A1↑, 2,   CYP2E1↑, 1,   Fenton↑, 1,   Ferroptosis↓, 1,   Ferroptosis↑, 3,   GPx↓, 2,   GPx4↓, 2,   GSH↓, 17,   GSH↑, 1,   GSH/GSSG↓, 2,   H2O2↑, 2,   HK1↓, 3,   HO-1↓, 1,   HO-1↑, 1,   ICD↑, 2,   Iron↑, 3,   lipid-P↑, 5,   MDA↑, 4,   NADH↓, 1,   NRF2↓, 2,   NRF2↑, 3,   OXPHOS↓, 10,   OXPHOS↑, 4,   OXPHOS↝, 2,   mt-OXPHOS↓, 4,   ROS↓, 5,   ROS↑, 92,   ROS⇅, 1,   ROS↝, 1,   mt-ROS↑, 3,   SOD↓, 3,   SOD↑, 1,   SOD1↓, 1,   Thiols↓, 1,   TrxR↓, 1,   xCT↓, 4,   xCT↑, 1,  

Metal & Cofactor Biology ⓘ

Zn2+↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 4,   ATP↓, 116,   ATP↑, 6,   ATP⇅, 1,   ATP↝, 2,   ATP∅, 2,   i-ATP↓, 2,   i-ATP↑, 1,   mt-ATP↓, 1,   compIII↓, 1,   compIII↑, 1,   ETC↓, 1,   Insulin↓, 1,   MEK↓, 1,   mitResp↓, 7,   mitResp↑, 1,   MMP↓, 38,   MMP↑, 2,   MPT↑, 1,   mtDam↑, 12,   OCR↓, 7,   OCR↑, 4,   PGC-1α↑, 1,   Raf↓, 2,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACLY↓, 1,   adiP↑, 1,   AKT1↓, 2,   ALAT↓, 1,   ALDOA↓, 1,   AminoA↓, 1,   AMP↑, 1,   AMPK↑, 10,   p‑AMPK↑, 2,   ATP:AMP↓, 1,   CAIX↓, 1,   cMyc↓, 8,   CYP3A4↓, 1,   ECAR↓, 6,   ENO1↓, 2,   FAO↓, 1,   FAO↑, 1,   FASN↓, 2,   FBPase↑, 1,   GAPDH↓, 4,   GLO-I↓, 1,   glucoNG↓, 1,   glucoNG↑, 1,   GlucoseCon↓, 24,   GlucoseCon↑, 1,   GLUT2↓, 1,   GlutaM↓, 2,   GlutMet↓, 1,   glyC↓, 1,   Glycolysis↓, 50,   HK2?, 1,   HK2↓, 36,   lactateProd↓, 26,   lactateProd↑, 1,   e-lactateProd↓, 1,   LDH↓, 10,   LDH↑, 1,   p‑LDH↓, 1,   LDHA↓, 14,   lipoGen↓, 1,   MCT4↓, 1,   MCU↓, 1,   NAD↓, 3,   NADPH↓, 4,   PDH↓, 5,   PDH↑, 2,   PDK1↓, 5,   PDK3↑, 1,   PFK↓, 6,   PFK1↓, 4,   PFK2↓, 1,   PFKP↓, 1,   PGK1↓, 2,   PGM1↓, 1,   PI3K/Akt↓, 2,   PKM1↑, 1,   PKM2↓, 17,   PKM2↑, 1,   POLD1↓, 1,   PPP↓, 2,   Pyruv↓, 1,   Pyruv↑, 1,   p‑S6↓, 1,   p‑S6K↓, 1,   SIRT1↓, 1,   SIRT1↑, 2,   SREBP1↓, 1,   TCA↓, 3,   TCA↑, 2,   Warburg↓, 12,   β-oxidation↓, 1,  

Cell Death ⓘ

Akt↓, 24,   Akt↑, 1,   p‑Akt↓, 3,   p‑Akt↑, 1,   Apoptosis?, 3,   Apoptosis↑, 45,   mt-Apoptosis↑, 1,   BAD↑, 1,   Bak↑, 1,   BAX↓, 2,   BAX↑, 6,   Bax:Bcl2↑, 4,   Bcl-2↓, 13,   Bcl-xL↓, 1,   Casp↑, 7,   Casp∅, 1,   Casp2↑, 1,   Casp3↓, 3,   Casp3↑, 22,   cl‑Casp3↑, 3,   Casp7↑, 3,   Casp8↑, 4,   Casp9↑, 10,   cl‑Casp9↑, 1,   CK2↓, 1,   Cyt‑c↓, 1,   Cyt‑c↑, 16,   DR4↑, 1,   Fas↑, 1,   Ferroptosis↓, 1,   Ferroptosis↑, 3,   GSDMC↑, 1,   GSDME-N↑, 1,   hTERT/TERT↓, 1,   iNOS↓, 1,   iNOS↑, 1,   JNK↓, 1,   JNK↑, 3,   p‑JNK↓, 1,   lysoMP↑, 1,   MAPK↓, 4,   MAPK↑, 3,   p‑MAPK↓, 1,   Mcl-1↓, 6,   MLKL↑, 1,   MOMP↑, 1,   Myc↓, 1,   Necroptosis↑, 2,   necrosis↑, 5,   p27↑, 4,   p38↑, 3,   Pyro↑, 2,   survivin↓, 6,   Telomerase↓, 3,   TumCD↑, 6,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 1,   FOXD3↑, 1,   HER2/EBBR2↓, 3,   SOX9↓, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

ac‑H3↑, 1,   ac‑H4↑, 1,   HATs↓, 1,   HATs↑, 1,   other↓, 2,   other↑, 3,   other↝, 2,   OV6↓, 1,   tumCV↓, 10,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   i-CRT↓, 1,   ER Stress↑, 10,   HSP27↓, 1,   HSP70/HSPA5↓, 1,   HSP72↓, 1,   HSP90↓, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

ATG3↑, 1,   ATG5↝, 1,   autoF↓, 2,   Beclin-1↓, 1,   Beclin-1↑, 2,   Beclin-1↝, 1,   p‑Beclin-1↑, 1,   BNIP3?, 1,   BNIP3↝, 1,   LAMP2↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   LC3B-II↑, 1,   LC3II↑, 3,   lysosome↓, 1,   lysosome↝, 1,   MitoP↑, 1,   p62↓, 4,   p62↑, 1,   TumAuto↑, 17,  

DNA Damage & Repair ⓘ

ATM↑, 1,   DNAdam↑, 18,   mt-DNAdam↑, 1,   DNMT1↓, 1,   P53↓, 1,   P53↑, 8,   P53↝, 1,   p‑P53↑, 1,   p53 Wildtype∅, 1,   PARP↓, 1,   PARP↑, 3,   cl‑PARP↓, 1,   cl‑PARP↑, 6,   cl‑PARP1↑, 1,   PCNA↓, 2,   TP53↓, 2,   TP53↑, 1,   γH2AX↑, 4,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 2,   CDK4↓, 3,   Cyc↓, 1,   cycA1/CCNA1↑, 1,   CycB/CCNB1↓, 2,   cycD1/CCND1↓, 7,   cycD1/CCND1↑, 1,   cycE/CCNE↓, 1,   cycE/CCNE↑, 1,   P21↓, 3,   P21↑, 5,   TumCCA↑, 28,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 3,   CD133↓, 2,   CD24↓, 1,   CD44↓, 2,   CSCs↓, 10,   CSCs↑, 1,   CSCsMark↓, 1,   CTSB↓, 1,   CTSD↓, 1,   CTSL↑, 1,   Diff↓, 1,   EMT↓, 12,   EpCAM↓, 1,   ERK↓, 6,   ERK↑, 2,   p‑ERK↓, 3,   FOXO3↑, 1,   FOXO4↓, 1,   Gli1↓, 2,   GSK‐3β↓, 1,   HDAC↓, 6,   HDAC2↓, 1,   HDAC3↓, 1,   HDAC4↓, 1,   HDAC8↓, 2,   IGF-1↓, 4,   IGF-1R↓, 2,   IGFBP1↑, 1,   IGFBP3↑, 1,   mTOR↓, 14,   p‑mTOR↓, 1,   p‑mTORC1↓, 1,   mTORC2↓, 1,   n-MYC↓, 1,   Nestin↓, 1,   NOTCH↓, 2,   NOTCH1↓, 1,   NOTCH1↑, 1,   P70S6K↓, 1,   p‑P70S6K↓, 1,   PI3K↓, 13,   PTCH1↓, 1,   PTEN↑, 3,   RAS↓, 1,   Shh↓, 1,   Smo↓, 2,   SOX2↓, 1,   STAT3↓, 6,   p‑STAT3↓, 1,   STAT5↓, 1,   p‑STAT5↓, 1,   TOP1?, 1,   TOP1↓, 2,   TRPM7↓, 1,   TumCG↓, 26,   TumCG↑, 2,   Wnt↓, 3,   Zn2+↑, 1,  

Migration ⓘ

CA↓, 1,   Ca+2↓, 1,   Ca+2↑, 15,   Ca+2↝, 1,   i-Ca+2↑, 1,   CD31↓, 1,   E-cadherin↑, 6,   ER-α36↓, 1,   FAK↓, 1,   p‑FAK↓, 2,   Fibronectin↓, 1,   Furin↓, 1,   GLI2↓, 1,   ITGB1↓, 1,   ITGB6↓, 1,   Ki-67↓, 3,   miR-203↑, 1,   MMP2↓, 7,   MMP3↓, 1,   MMP9↓, 9,   MMP9↑, 1,   MMPs↓, 4,   MUC4↓, 1,   N-cadherin↓, 1,   PDGF↓, 1,   PKA↓, 2,   PKCδ↓, 1,   Rho↓, 2,   p‑RIP3↑, 1,   ROCK1↓, 1,   Slug↓, 2,   SMAD2↓, 1,   SMAD3↓, 1,   Snail↓, 5,   SPARC↑, 1,   STAC2↓, 1,   TGF-β↓, 5,   TIMP1↓, 1,   TIMP1↑, 2,   Treg lymp↓, 1,   TumCA↑, 1,   TumCI↓, 9,   TumCMig↓, 10,   TumCP↓, 28,   TumMeta↓, 10,   uPA↓, 3,   uPAR↓, 1,   Vim?, 1,   Vim↓, 2,   Zeb1↓, 3,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 7,   EGFR↓, 6,   eNOS↓, 1,   eNOS↑, 1,   EPR↑, 1,   HIF-1↓, 4,   Hif1a↓, 19,   NO↑, 4,   VEGF↓, 14,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   CellMemb↑, 1,   CTR1↑, 1,   GLUT1↓, 18,   GLUT4↓, 4,   NHE1↓, 1,   P-gp↓, 3,   P-gp↑, 1,   SVCT-2∅, 1,  

Immune & Inflammatory Signaling ⓘ

CCR7↓, 1,   COX2↓, 9,   CRP↓, 1,   CXCR4↓, 1,   DCells↑, 1,   HMGB1↓, 1,   HMGB1↑, 1,   i-HMGB1↓, 1,   IFN-γ↓, 1,   IFN-γ↑, 1,   IL1↓, 1,   IL10↓, 2,   IL12↑, 1,   IL17↓, 1,   IL1β↓, 2,   IL2↑, 1,   IL4↓, 1,   IL6↓, 4,   IL8↓, 1,   Inflam↓, 5,   JAK↓, 1,   JAK2↓, 2,   pol-M1↑, 1,   M2 MC↓, 1,   pol-M2 MC↓, 1,   MCP1↓, 1,   NF-kB↓, 14,   p65↓, 2,   PD-1↓, 1,   PD-L1↓, 2,   PGE2↓, 3,   PSA↓, 2,   Th1 response↑, 1,   TLR4↓, 1,   TNF-α↓, 4,  

Cellular Microenvironment ⓘ

i-pH↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 3,   CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 7,   BioAv↑, 8,   BioAv↝, 5,   ChemoSen↓, 2,   ChemoSen↑, 24,   CYP1A2↑, 1,   CYP2A3/CYP2A6↓, 1,   Dose?, 1,   Dose↓, 2,   Dose↑, 4,   Dose↝, 11,   Dose∅, 3,   eff↓, 16,   eff↑, 57,   eff↝, 5,   Half-Life↓, 2,   Half-Life↝, 1,   P450↓, 1,   RadioS↑, 7,   selectivity↑, 25,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AR↓, 3,   AST↓, 1,   BG↓, 2,   BloodF↑, 1,   BMD↑, 1,   CRP↓, 1,   EGFR↓, 6,   GutMicro↑, 2,   HER2/EBBR2↓, 3,   hTERT/TERT↓, 1,   IL6↓, 4,   Ki-67↓, 3,   LDH↓, 10,   LDH↑, 1,   p‑LDH↓, 1,   Myc↓, 1,   PD-L1↓, 2,   PSA↓, 2,   TP53↓, 2,   TP53↑, 1,  

Functional Outcomes ⓘ

AntiCan↑, 8,   AntiTum↑, 2,   cardioP↑, 2,   chemoP↑, 1,   ChemoSideEff↓, 2,   hepatoP↑, 1,   neuroP↑, 2,   OS↑, 5,   QoL↑, 1,   Risk↓, 3,   toxicity↓, 5,   toxicity↑, 1,   toxicity↝, 3,   toxicity∅, 2,   TumVol↓, 3,   TumW↓, 1,   Weight∅, 1,  

Infection & Microbiome ⓘ

CD8+↑, 3,  
Total Targets: 491

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 17,   Catalase↑, 9,   Ferroptosis↓, 1,   GPx↑, 8,   GPx1↑, 1,   GSH↓, 1,   GSH↑, 9,   GSR↓, 1,   GSR↑, 1,   GSTs↑, 2,   H2O2↓, 3,   HO-1↑, 7,   Keap1↓, 2,   lipid-P↓, 9,   mt-lipid-P↓, 1,   MDA↓, 4,   MDA↑, 1,   Mets↝, 1,   MPO↓, 1,   NADPH/NADP+↑, 1,   NQO1↑, 1,   Nrf1↑, 1,   NRF2↑, 11,   OXPHOS↑, 3,   PARK2↑, 2,   Prx↓, 1,   Prx↑, 1,   ROS↓, 30,   ROS↑, 3,   ROS∅, 2,   mt-ROS↓, 1,   mt-ROS↑, 1,   SAM-e↑, 1,   SOD↑, 8,   SOD1↑, 2,   SOD2↑, 1,   Trx↑, 1,   VitC↑, 2,   VitE↑, 2,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↓, 1,   ATP↓, 3,   ATP↑, 32,   ATP↝, 1,   ATP∅, 1,   mt-ATP↑, 1,   mitResp↑, 4,   MMP↓, 3,   MMP↑, 6,   mtDam↓, 3,   mt-OCR↑, 1,   PGC-1α↑, 5,   PINK1↑, 1,  

Core Metabolism/Glycolysis ⓘ

Acetyl-CoA↑, 1,   AMPK↓, 1,   AMPK↑, 5,   CREB↑, 1,   ECAR↑, 1,   ECAR∅, 1,   FAO↑, 2,   FASN↓, 1,   G6PD↑, 1,   glucoNG↓, 1,   glucose↓, 1,   GlucoseCon↓, 1,   GlucoseCon↑, 3,   Glycolysis↓, 1,   Glycolysis↑, 2,   Glycolysis↝, 1,   HK2↓, 1,   homoC↓, 1,   lactateProd↓, 1,   LDH↓, 2,   LDHA↓, 1,   LDHB↑, 1,   NAD↑, 1,   NAD↝, 1,   NADH:NAD↑, 1,   NADPH↓, 3,   NADPH↑, 2,   NH3↑, 1,   PFK2↓, 1,   PGM1?, 1,   PKM2↓, 1,   PPARα↑, 2,   PPARγ↑, 2,   PPP↓, 1,   SIRT1↑, 3,   TCA↑, 1,  

Cell Death ⓘ

Akt↓, 2,   Akt↑, 1,   Apoptosis↓, 5,   BAX↑, 2,   Bax:Bcl2↓, 1,   Bcl-2↓, 2,   Bcl-2↑, 1,   Casp3↓, 2,   Casp3↑, 2,   Casp9↓, 1,   Casp9↑, 1,   Cyt‑c↓, 1,   Cyt‑c∅, 1,   Ferroptosis↓, 1,   iNOS↓, 3,   p‑JNK↓, 1,   MAPK↓, 2,   p38↓, 1,   YAP/TEAD↑, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 3,   other?, 1,   other↑, 4,   other↝, 3,  

Protein Folding & ER Stress ⓘ

GRP78/BiP↑, 1,   HSP70/HSPA5↝, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   LC3II↑, 1,   MitoP↑, 2,   p62↓, 1,   p62↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

Diff↑, 1,   FOXO↑, 1,   FOXO3↑, 1,   GSK‐3β↓, 3,   mTOR↓, 1,   p‑mTOR↑, 1,   PI3K↓, 2,   RAS↓, 1,   STAT↓, 1,   Wnt↑, 1,  

Migration ⓘ

AntiAg↑, 1,   APP↓, 4,   Ca+2↓, 1,   Ca+2↑, 2,   Ca+2↝, 2,   Cartilage↑, 1,   FAK↑, 1,   MMP9↓, 1,   PKA↑, 1,   serineP↓, 1,   SMAD3↓, 1,   TGF-β↓, 1,   TIMP1↓, 1,   TumCP↓, 1,   VCAM-1↓, 1,   Vim↓, 1,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,   NO↓, 2,   VEGF↑, 1,  

Barriers & Transport ⓘ

BBB↓, 1,   BBB↑, 5,   BBB↝, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   CRP↓, 1,   IL10↓, 1,   IL17↓, 1,   IL1β↓, 7,   IL2↓, 1,   IL33↓, 1,   IL4↓, 1,   IL6↓, 6,   IL8↓, 3,   INF-γ↓, 1,   Inflam↓, 22,   NF-kB↓, 6,   NF-kB↑, 1,   p‑NF-kB↓, 1,   p65↓, 1,   PGE2↓, 1,   TLR4↓, 1,   TNF-α↓, 9,   VitD↑, 1,  

Synaptic & Neurotransmission ⓘ

5HT↑, 1,   AChE↓, 1,   BDNF↑, 3,   ChAT↑, 2,   tau↓, 1,   p‑tau↓, 5,   TrkB↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 16,   BACE↓, 5,   NLRP3↓, 2,  

Hormonal & Nuclear Receptors ⓘ

ER(estro)↓, 1,   testos↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 2,   BioAv↝, 2,   BioEnh↑, 1,   Dose↑, 1,   Dose↝, 4,   eff↓, 2,   eff↑, 8,   eff↝, 1,   Half-Life↓, 1,   Half-Life↝, 2,   P450↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

BG↓, 1,   BloodF↑, 1,   BMD↑, 3,   BMPs↑, 1,   BP↓, 1,   BP∅, 1,   Calcium↑, 1,   CRP↓, 1,   GutMicro↑, 1,   hs-CRP↓, 1,   IL6↓, 6,   LDH↓, 2,   Mag↑, 1,   NOS2↓, 1,   VitD↑, 1,  

Functional Outcomes ⓘ

AntiAge↑, 2,   AntiDiabetic↑, 2,   Bone Healing↑, 1,   cardioP↑, 4,   CardioT↓, 1,   chemoP↑, 1,   chemoPv↑, 1,   ChemoSideEff↓, 1,   cognitive↑, 13,   hepatoP↑, 4,   memory↑, 10,   Mood↑, 1,   motorD↓, 1,   motorD↑, 3,   neuroP↑, 16,   radioP↑, 1,   RenoP↑, 1,   Risk↓, 3,   Strength↑, 1,   toxicity↓, 3,   toxicity↑, 1,   toxicity↝, 2,   toxicity∅, 3,   Wound Healing↑, 1,  

Infection & Microbiome ⓘ

AntiFungal↑, 1,   AntiViral↑, 1,   Bacteria↓, 2,   Sepsis↓, 1,  
Total Targets: 242

Scientific Paper Hit Count for: ATP, Adenosine triphosphate
11 3-bromopyruvate
9 Magnetic Fields
9 Vitamin C (Ascorbic Acid)
6 Berberine
6 Shikonin
5 Silver-NanoParticles
5 Alpha-Lipoic-Acid
5 Citric Acid
5 Quercetin
5 salinomycin
4 Ashwagandha(Withaferin A)
4 Graviola
4 Resveratrol
3 2-DeoxyGlucose
3 Apigenin (mainly Parsley)
3 Capsaicin
3 Propolis -bee glue
3 diet FMD Fasting Mimicking Diet
3 EGCG (Epigallocatechin Gallate)
3 Honokiol
3 Luteolin
3 Melatonin
3 Rosmarinic acid
3 Sulforaphane (mainly Broccoli)
3 Silymarin (Milk Thistle) silibinin
3 Ursolic acid
3 Urolithin
2 Radiotherapy/Radiation
2 Allicin (mainly Garlic)
2 Copper and Cu NanoParticles
2 Curcumin
2 Docosahexaenoic Acid
2 Chemotherapy
2 Galloflavin
2 Hydrogen Gas
2 Metformin
2 Pachymic acid
2 Phenethyl isothiocyanate
2 Thymoquinone
2 Vitamin B5,Pantothenic Acid
2 Vitamin K2
1 Sorafenib (brand name Nexavar)
1 cetuximab
1 Anthocyanins
1 Auranofin
1 Acetyl-l-carnitine
1 Andrographis
1 doxorubicin
1 Artemisinin
1 Aloe anthraquinones
1 Betulinic acid
1 Boron
1 Boswellia (frankincense)
1 Chrysin
1 Disulfiram
1 Emodin
1 Electrical Pulses
1 Ferulic acid
1 Hyperthermia
1 Ivermectin
1 Methylene blue
1 MCToil
1 immunotherapy
1 Magnesium
1 Methylglyoxal
1 Pterostilbene
1 Radio Frequency
1 EMF
1 SonoDynamic Therapy UltraSound
1 triptolide
1 Vitamin B1/Thiamine
1 Vitamin B12
1 Folic Acid, Vit B9
1 Vitamin B2,Riboflavin
1 Arsenic trioxide
1 probiotics
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#:21  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

Home Page