Iron Cancer Research Results

Iron, Iron: Click to Expand ⟱
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Iron is an essential nutrient that is crucial for various cellular processes, including DNA synthesis, cell proliferation, and oxygen transport.
Cancer cells often have increased iron requirements due to their rapid growth and proliferation. Some tumors can acquire iron through various mechanisms, including upregulating iron transport proteins. This can support their growth and survival.
Excess iron can lead to the production of reactive oxygen species (ROS) through Fenton reactions, which can cause oxidative damage to DNA, proteins, and lipids. This oxidative stress can contribute to cancer development and progression.
Scientific Papers found: Click to Expand⟱
3284- ALA,    Alpha-Lipoic Acid Mediates Clearance of Iron Accumulation by Regulating Iron Metabolism in a Parkinson's Disease Model Induced by 6-OHDA
- vitro+vivo, Park, NA
*antiOx↑, naturally occurring enzyme cofactor with antioxidant and iron chelator properties and has many known effects. ALA has neuroprotective effects on PD.
*IronCh↑,
*neuroP↑,
*ROS↓, decreasing the levels of intracellular reactive oxygen species and iron.
*Iron↓,
*BBB↑, ALA also provides neuroprotection against PD because it can penetrate the blood–brain barrier.
*motorD↑, ALA ameliorates motor behavior and prevents DA neuron loss in the SN of PD rat models.
*GSH↑, ALA Inhibits the Decrease in the Activity of SOD and GSH in the SN of a Rat Model of PD Induced by 6-OHDA

1076- ART/DHA,    The Potential Mechanisms by which Artemisinin and Its Derivatives Induce Ferroptosis in the Treatment of Cancer
- Review, NA, NA
Ferroptosis↑,
ROS↑, interaction between heme-derived iron and ART will result in the production of ROS
ER Stress↑,
i-Iron↓, DHA can cause intracellular iron depletion in a time- and dose-dependent manner
TumAuto↑,
AMPK↑,
mTOR↑,
P70S6K↑,
Fenton↑,
lipid-P↑,
ROS↑,
ChemoSen↑, combination of ART and Nrf2 inhibitors to promote ferroptosis may have more efficient anticancer effects without damaging normal cells.
NRF2↑, Liu et al. discovered that ART covalently targets Keap1 at Cys151 to activate the Nrf2-dependent pathway [94
NRF2↓, inhibition of Nrf2-related gene expression accelerated erastin and sorafenib-induced ferroptosis [45]. More importantly, an accumulating body of research suggests that ART may induce ferroptosis in cancer cells by regulating the above molecules.

5132- ART/DHA,    Dihydroartemisinin Exerts Its Anticancer Activity through Depleting Cellular Iron via Transferrin Receptor-1
- in-vitro, Liver, HepG2 - in-vitro, BC, MCF7
Iron↓, In the current study, we found that dihydroartemisinin caused cellular iron depletion in time- and concentration-dependent manners.
TfR1/CD71↓, Moreover, dihydroartemisinin reduced the level of transferrin receptor-1 associated with cell membrane.
ROS↑, which may be a new action mechanism of DHA independently of oxidative damage.

5883- CAR,    Safety and tolerability of carvacrol in healthy subjects: a phase I clinical study
- Trial, Nor, NA
*Dose↝, Subjects were randomly divided into two groups receiving 1 and 2 mg/kg/day carvacrol.
*HDL↓, There was significant reductions in high-density lipoprotein cholesterol (HDL), total bilirubin, amylase, iron, red blood cells (RBC) count, and HCT after one-month treatment with 2 mg/kg/day carvacrol
*Bil↓,
*Iron↓,
*toxicity↓, The results of this phase I study regarding carvacrol effects on healthy subjects, showed clinical safety and tolerability for this agent.

1633- HCA,    Hydroxycitric Acid Alleviated Lung Ischemia-Reperfusion Injury by Inhibiting Oxidative Stress and Ferroptosis through the Hif-1α Pathway
- in-vivo, NA, NA - in-vitro, Nor, HUVECs
*other↓, HCA effectively attenuated lung injury, inflammation, and edema induced by ischemia reperfusion
*Inflam↓,
*MDA↓, HCA treatment significantly reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels
*ROS↓,
*Iron↓, while decreasing iron content and increasing superoxide dismutase (SOD)
*SOD↓,
*Hif1a↓, HCA administration significantly inhibited Hif-1α and HO-1 upregulation both in vivo and in vitro.
*HO-1↓,

4213- Hup,    Huperzine A-Liposomes Efficiently Improve Neural Injury in the Hippocampus of Mice with Chronic Intermittent Hypoxia
- in-vivo, NA, NA
*cognitive↑, HuA-LIP significantly ameliorated cognitive dysfunction and neuronal damage in CIH mice.
*SOD↑, HuA-LIP elevated T-SOD and GSH-Px abilities and decreased MDA content to resist oxidative stress damage induced by CIH.
*GPx↑,
*MDA↓,
*ROS↓,
*Iron↓, HuA-LIP reduced brain iron levels by downregulating TfR1, hepcidin, and FTL expression.
*TfR1/CD71↓,
*FTL↓,
*ERK↑, HuA-LIP activated the PKAα/Erk/CREB/BDNF signaling pathway and elevated MAP2, PSD95, and synaptophysin to improve synaptic plasticity.
*PKA↑,
*CREB↑,
*BDNF↑,
*PSD95↑,
*neuroP↑, HuA-LIP showed a superior performance against neuronal damage induced by CIH.

4209- Hup,    Huperzine A, reduces brain iron overload and alleviates cognitive deficit in mice exposed to chronic intermittent hypoxia
- in-vivo, NA, NA
*ROS↓, HuA improves synaptic plasticity and decreases ROS level in CIH mice
*cognitive↑, HuA significantly improved cognitive impairment and neuronal damage in the hippocampus of CIH mice via increasing the ratio of Bcl-2/Bax and inhibiting caspase-3 cleavage.
*neuroP↑,
*Bax:Bcl2↓,
*Casp3↑,
*NADPH↓, HuA considerably decreased ROS levels by downregulating the high levels of NADPH oxidase (NOX 2, NOX 4) mediated by CIH.
*NOX↓,
*TfR1/CD71↓, Decreased levels of TfR1 and FTL proteins observed in HuA treated CIH group, could reduce iron overload in hippocampus. HuA increased PSD 95 protein expression, CREB activation and BDNF protein expression
*Iron↓,
*PSD95↑,
*BDNF↑,

7562- HYP,  doxoR,    Hyperoside Inhibits Doxorubicin-Induced Ferroptosis in Cardiomyocytes via the Nrf2/GPX4 Pathway
- in-vivo, Nor, NA
*ROS↓, Hyperoside (Hyp) exhibits notable protective effects by targeting oxidative stress, ferroptosis, and apoptosis.
*Ferroptosis↓,
*Apoptosis↓,
*cardioP↑, Hyp co-administration mitigated doxorubicin-induced cardiac impairment in mice, demonstrated by enhanced ejection fraction (EF) and fractional shortening (FS), diminished inflammatory cell infiltration and fibrotic changes
*MDA↓, Hyp reduced oxidative stress (lower MDA, higher SOD and GSH-Px activity), inhibited ferroptosis (decreased intracellular Fe2 + , MDA, 4-HNE, PTGS2, and ASCL4; increased GSH and Ferritin),
*SOD↑,
*GPx↑,
*i-Iron↓,
*4-HNE↓,
*GSH↑,
*Ferritin↑,
*ACSL4↓,
*NRF2↑, Mechanistically, Hyp activated the Nrf2/GPX4 axis: it promoted Nrf2 nuclear translocation, upregulated GPX4 expression as shown by molecular docking.
*GPx4↑,

7698- IP6,    Dietary Phytic Acid, Dephytinization, and Phytase Supplementation Alter Trace Element Bioavailability-A Narrative Review of Human Interventions
- Review, Nor, NA
*Iron↓, Most phytic acid-rich food-feeding studies (13 of 17, 77%) showed compromised iron and zinc bioavailability.
*Zn2+↓,
*other↝, Conclusions: Strong evidence supports decreased iron and zinc bioavailability in phytic acid-rich diets and significant improvements with phytase interventions.
*IronCh↑, Phytic acid is a potent chelating agent, capable of binding to essential micronutrients such as zinc, iron, calcium, manganese, and magnesium

7700- IP6,    A84 THE USE OF PHYTASE TO ENHANCE DIETARY IRON AND ZINC ABSORPTION - A SCOPING REVIEW
- Review, Nor, NA
*Iron↓, Strong evidence supports decreased iron and zinc bioavailability in phytic acid-rich diets and the improvement potential with phytase interventions.
*eff↑, Phytases are enzymes that break down phytic acid, releasing micronutrients and enhancing their bioavailability, particularly iron and zinc.

7766- ISL,    Isoliquiritigenin alleviates myocardial ischemia-reperfusion injury by regulating the Nrf2/HO-1/SLC7a11/GPX4 axis in mice
- in-vivo, Stroke, NA
*ROS↓, ISL significantly attenuated H/R-triggered production of reactive oxygen species in NMCM, reduced the expression of malondialdehyde and the activity of lactate dehydrogenase, enhanced superoxide dismutase and catalase activity,
*MDA↓,
*LDH↑,
*SOD↑,
*Catalase↑,
*NRF2↑, and increased the expression of nuclear factor E2-related factor 2 (Nrf2) and its downstream heme oxygenase 1 (HO-1), thereby mitigating oxidative stress damage.
*i-Iron↓, ISL reduced intracellular free iron accumulation, up-regulated glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) expression, and inhibited lipid peroxidation accumulation, thereby alleviating ferroptosis.
*GPx4↑,
*xCT/SLC7A11↑,
*lipid-P↓,
*Ferroptosis↓,
*HO-1↑, ISL treatment increased the levels of HO-1, GPX4, and SLC7A11, inhibited the expression of ACSL4
*ACSL4↓,
*mtDam↓, alleviated mitochondrial damage, and ferroptosis, ultimately reducing myocardial infarction area and injury induced by I/R.
*Stroke↓,

8055- KAE,    Molecular Mechanisms of the Anticancer Activity of the Flavonoid Kaempferol: A Comprehensive Review
- Review, Var, NA
antiNeop↑, Kaempferol (KAE), a natural flavonoid, has emerged as a promising multi-target antineoplastic agent characterized by high efficacy and minimal systemic toxicity.
*toxicity↓,
TumCCA↑, KAE orchestrates tumor eradication by enforcing cell cycle arrest across multiple phases and triggering a complex, interconnected network of programmed cell death.
ROS↑, We highlight how reactive oxygen species and endoplasmic reticulum stress serve as central upstream nodes driving the mechanistic crosstalk among apoptosis, lethal autophagy, gasdermin E-mediated pyroptosis, and ferroptosis.
ER Stress↑,
TumAuto↑,
Pyro↑,
Ferroptosis↑,
angioG↓, KAE actively remodels the tumor microenvironment by inhibiting angiogenesis and repolarizing tumor-associated macrophages, thereby converting immunosuppressive "cold" tumors into immune-active "hot" tumors.
Imm↝,
eff↑, this review introduces the emerging prebiotic-like crosstalk between KAE and the gut microbiome, providing a strong mechanistic rationale for its synergistic application with immune checkpoint inhibitors.
ChemoSen↑, As a potent chemosensitizer, KAE also overcomes multidrug resistance and mitigates chemotherapy-induced toxicities.
MPT↑, This leads to the opening of the mitochondrial permeability transition (MPTP) pore and the collapse of the mitochondrial membrane potential (ΔΨm).
MMP↓,
mtDam↑, damaged mitochondria release pro-apoptotic factors, including cytochrome c, into the cytoplasm, inducing the formation of the apoptosome.
Cyt‑c↑,
Bax:Bcl2↑, upregulation of the Bax/Bcl-2 ratio.
Fas↑, demonstrated that in colorectal cancer models, KAE treatment significantly upregulates the expression of membrane-bound FAS ligand.
DR4↑, KAE directly upregulates the expression of death receptor 4 and death receptor 5 in human ovarian cancer cells (OVCAR-3 and SKOV-3) by activating the JNK/ERK-CHOP signaling pathway.
DR5↑,
JNK↑,
ERK↑,
CHOP/DDIT3↑,
ER Stress↑, Studies have shown that KAE possesses significant ERS-inducing activity, leading to the pathological accumulation of unfolded or misfolded proteins within the endoplasmic reticulum (ER) lumen, which in turn triggers a persistent unfolded protein resp
UPR↑,
Ca+2↑, accumulated cytosolic Ca²+ acts as a central apoptotic signal
PI3K↓, The inhibition of the PI3K/Akt/mTOR pathway is a primary mechanism for this effect.
Akt↓,
mTOR↓,
AMPK↑, Conversely, KAE reactivates the AMPK pathway.
*Ferroptosis↓, KAE acts as a potent antioxidant in normal tissues to prevent ferroptosis-induced injury.
*antiOx↑,
*NRF2↑, KAE effectively suppresses ferroptosis by strongly activating the Nrf2/glutathione peroxidase 4 (GPX4) antioxidant axis.
*GPx4↑,
*ROS↓, It actively reduces intracellular ROS, malondialdehyde, and iron (Fe²+) accumulation while upregulating the protective SLC7A11 transporter
*MDA↓,
*i-Iron↓,
*xCT/SLC7A11↑,
VEGF↓, KAE not only inhibits VEGF expression driven by hypoxia-inducible factor-1α (HIF-1α) but also simultaneously blocks the Wnt/β-catenin signaling pathway and the epithelial-mesenchymal transition (EMT) process
Wnt↓,
β-catenin/ZEB1↓,
EMT↓,
STAT3↓, KAE blocks the persistent activation of the STAT3 signaling pathway, leading to the downregulation of M2 phenotypic markers and the inhibition of the inflammatory chemokine CCL2 release.
M2 MC↓,
MCP1/CCL2↓,
MMP9↓, thereby downregulating the protein expression and enzymatic activity of MMP-9.
MMP2↓, in tongue squamous cell carcinoma models, KAE inhibits the expression of MMP-2 and its tissue inhibitor, TIMP-2, at the transcriptional level
TIMP2↓,
ChemoSen↑, When combined with classical chemotherapeutics, KAE functions as a potent sensitizer, amplifying the lethal effects of the drugs through complementary signaling networks.
PKM2↑, In colorectal cancer cells, KAE promotes the expression of microRNA-326 (miR-326), which directly targets the 3′-UTR of the pyruvate kinase M2 (PKM2) isoform to inhibit glycolysis.
Glycolysis↓,
CSCs↓, profound chemosensitizing effect by downregulating core stemness transcription factors (such as SOX2 and OCT4) and disrupting the CD44-NANOG-MDR1 resistance complex
SOX4↓,
OCT4↓,
CD44↓,
Nanog↓,
MDR1↓,
*GutMicro↑, KAE exerts a remarkable prebiotic-like effect by remodeling the architectural composition of the gut microbiota

8225- LCA,  Cisplatin,    Licochalcone A protects against cisplatin-induced acute kidney injury via the modulation of Nrf2/Keap1-mediated ferroptosis and apoptosis
- in-vivo, Nor, NA
*RenoP↑, Lico A treatment significantly ameliorated CP-induced AKI, accompanied by reduced serum levels of urea nitrogen and creatinine, downregulated expression of kidney injury molecule-1 and neutrophil-gelatinase-associated lipocalin, and attenuated renal
*Urea↓,
*BUN↓,
*creat↓,
*Apoptosis↓, Lico A reduced CP-triggered renal apoptosis and the expression of apoptosis-related proteins.
*Ferroptosis↓, Lico A mitigated ferroptosis by suppressing iron overload, oxidative stress, lipid peroxidation and mitochondrial dysfunction.
*Iron↓,
*ROS↓,
*lipid-P↓,
*mtDam↓,
*NRF2↑, Lico A also markedly activated nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) signaling

8130- LF,    Lactoferrin targeting INTL1 receptor inhibits hepatocellular carcinoma progression via apoptosis and cell cycle signaling pathways
- in-vitro, HCC, HepG2 - in-vitro, HCC, HepG3 - in-vitro, HCC, SK-HEP-1
Iron↓, Lactoferrin (LF), a natural iron-binding glycoprotein with reported anticancer effects,
TumCP↓, Data showed that LF exerted anti-proliferative effects on HepG2, Hep3B, and SK-Hep1 cells while having no cytotoxicity on healthy liver cells (FL83B).
selectivity↑,
TumCCA↑, Mechanistically, LF induces mitochondrial-mediated apoptosis and G0/G1 cell cycle arrest in HepG2 cells, associated with increased phosphorylation of p38 MAPK and JNK for apoptosis, and ERK phosphorylation for cell cycle arrest
p‑MAPK↑,
JNK↑,
Apoptosis↑,

8131- LF,    Molecular mechanism of inhibitory effects of bovine lactoferrin on the growth of oral squamous cell carcinoma
- in-vitro, OS, HSC2 - in-vitro, OS, HSC3 - in-vitro, OS, HSC4 - in-vitro, Nor, RT7
P53↑, We found that bLF (1, 10, and 100 μg/ml) induced activation of p53,
Akt↓, bLF downregulated the phosphorylation of Akt and activated suppressor of cytokine signaling 3 (SOCS3), thereby attenuating multiple signaling pathways including mTOR/S6K and JAK/STAT3.
SOCS-3↑,
mTOR↓,
JAK↓,
STAT3↓,
selectivity↑, we revealed that bLF exerted its effect selectively against HSC3 but not on RT7 via different effects on the phosphorylation status of NF-κB and Akt.
TumCP↓, first report showing that bLF selectively suppresses proliferation through mTOR/S6K and JAK/STAT3 pathways and induction of apoptosis in OSCC.
Iron↓, Lactoferrin (LF), an 80-kDa member of the transferrin family of iron binding glycoproteins [1], is naturally produced by epithelial cells [2] and found in external secretions mainly in milk
TumCCA↑, Recent studies have shown that LF directly arrested cell cycle in G1/S transition in breast and head and neck cancers both in vitro and in vivo

8132- LF,    Lactoferrin selectively triggers apoptosis in highly metastatic breast cancer cells through inhibition of plasmalemmal V-H+-ATPase
- in-vitro, BC, HS587T - in-vitro, BC, MDA-MB-231 - in-vitro, BC, T47D - in-vitro, BC, MCF10
Iron↓, Lactoferrin (Lf) is a natural pro-apoptotic iron-binding glycoprotein with strong anticancer activity whose mechanism of action is not fully understood.
AntiCan↑,
Apoptosis↑, Here, we show that bovine Lf (bLf) preferentially induces apoptosis in the highly metastatic breast cancer cell lines Hs 578T and MDA-MB-231,
selectivity↑, which display a prominent localisation of V-H+-ATPase at the plasma membrane, but not in the lowly metastatic T-47D or in the non-tumorigenic MCF-10-2A cell lines.
ECAR↓, bLf decreases the extracellular acidification rate and causes intracellular acidification in metastatic breast cancer cells
i-pH↑,
ATPase↓, Bovine lactoferrin inhibits both the proton pumping and hydrolytic activities of V-H+-ATPase

8134- LF,    Bovine lactoferrin and lactoferricin exert antitumor activities on human colorectal cancer cells (HT-29) by activating various signaling pathways
- in-vitro, CRC, HT-29
Iron↓, Lactoferrin (Lf) is an iron-binding glycoprotein that is present at high concentrations in milk.
Apoptosis↑, . bLf and LfcinB significantly induced apoptosis in HT-29 cells but not in normal human intestinal epithelial cells,
selectivity↑,
Casp8↑, expression of caspase 8, p53,306 and p21 was markedly upregulated by bLf and LfcinBs, implying that bLf and307 LfcinBs trigger these two pathways to exert their antitumor activities.
P53↑,
P21↑,

1777- MEL,    Melatonin as an antioxidant: under promises but over delivers
- Review, NA, NA
*ROS↓, uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances
*Fenton↓, reportedly chelates transition metals, which are involved in the Fenton/Haber-Weiss reactions
*antiOx↑, credible evidence to suggest that melatonin should be classified as a mitochondria-targeted antioxidant
*toxicity∅, uncommonly high-safety profile of melatonin also bolsters this conclusion.
*GPx↑, melatonin was found to stimulate antioxidative enzymes including glutathione peroxidase and glutathione reductase
*GSR↑,
*GSH↑, melatonin upregulates the synthesis of glutathione
*NO↓, neutralize nitrogen-based toxicants, i.e., nitric oxide
*Iron↓, Melatonin chelates both iron (III) and iron (II), which is the form that participates in the Fenton reaction to generate the hydroxyl radical
*Copper↓, copper-chelating ability of melaton
*IL1β↓, significant reductions in plasma cardiac troponin 1, interleukin 1 beta, inducible nitric oxide synthase (iNOS) and caspase 3 due to melatonin
*iNOS↓,
*Casp3↓,
*BBB↑, melatonin readily crosses the blood-brain barrier;
*RenoP↑, Published reports haveshown that the lung,231, 232 liver, 233- 235 kidney,236 pancreas,237 intestine,238 urinary bladder,239,240 corpus cavernosum,241 skeletal muscle242, 243 spinal cord244, 245 and stem cells246 are alsoprotected by melatonin.
chemoP↑, Melatonin has not been found to interfere with the efficacy of prescription drugs. Doxorubicin, if given it in combination with melatonin may allow the use of a larger dose with greater efficacy.
*Ca+2↝, Moreover, melatonin regulates free Ca2+ movement intracellularly
eff↑, elatonin was found to exaggerate the cancer inhibiting actions of pitavastatin270 and pravastatin271 against breast cancer in experimental studies
*PKCδ?, major targets by which melatonin reduces methamphetamine-related neuronal damage is due to the inhibition of the PKCδ gene
ChemoSen↑, at least some cases melatonin reduces the toxicity of these pharmacological agents in normal cells256, 289, 290 while enhancing the cancer-killing actions (also, see below) of conventional chemotherapeutic agents.256, 291-293
eff↑, TRAIL was combined with melatonin for the treatment of A172 and U87 human glioblastoma cells, however, apoptotic cell death was greatly exaggerated over that caused by TRAIL alone
Akt↓, in GBM: observed effect was related to a modulation of protein kinase c which reduced Akt activation resulting in a rise in death receptor 5 (DR5) levels;
DR5↑,
selectivity↑, The pro-oxidant action of melatonin is common in cancer cells while in normal cells the indoleamine is a powerful antioxidant.
ROS↑, cancer cells
eff↑, human lung adenocarcinoma cells (SK-LV-1) showed that melatonin also increased their sensitivity to the chemotherapy, cisplatin.

7828- Myr,  MBS,    Neuroprotective Potential of Mung Bean (Vigna radiata L.) Polyphenols in Alzheimer's Disease: A Review
- Review, AD, NA
*BBB↑, myricetin was able to cross the BBB, and thus exhibited neuroprotective activity in AD.
*neuroP↑,
*cognitive↑, myricetin (10 mg/kg, i.p.) improved the cognitive deficits and increased the density of hippocampal CA3 pyramidal neurons of STZ-injected (i.c.v.) rats
*Aβ↓, myricetin reduced the production of Aβ peptides by enhancing the activity of α-secretase (ADAM10) and βsecretase (BACE-1).
*ADAM10↑,
*BACE/β-secretase↝,
*IronCh↑, myricetin chelated mental irons and inhibited iron uptake into the brain, thus inhibiting excessive metal-induced Aβ aggregation
*Iron↓,
*AChE↓, inhibitory effect of myricetin on AChE in a model induced by injection (i.p.) of scopolamine, a neurotoxin that could easily penetrate BBB
*ROS↓, suppressing Aβ production and aggregation, oxidative stress, and AChE activity

5026- QC,    Quercetin induces ferroptosis in gastric cancer cells by targeting SLC1A5 and regulating the p-Camk2/p-DRP1 and NRF2/GPX4 Axes
- in-vitro, GC, NA
SLC1A5↓, We demonstrated that Quer inhibits SLC1A5 expression
ROS↑, we found that Quer altered the intracellular ROS levels, antioxidant system protein expression levels, and iron content.
Iron↓, Quer increased the intracellular iron content by inhibiting SLC1A5
NRF2↓, Mechanistically, Quer binds to SLC1A5, inhibiting the nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), resulting in decreased xCT/GPX4 expression.
GPx4↓,
Ferroptosis↑, These three changes collectively led to ferroptosis in GC cells

2343- QC,    Pharmacological Activity of Quercetin: An Updated Review
- Review, Nor, NA
*ROS↓, Quercetin is a potent scavenger for ROS and hence protects the body against oxidative stress
*GSH↑, Studies of animals and cells have shown that the synthesis of GSH is induced by quercetin.
*Catalase↑, increased expression of superoxide dismutase (SOD), catalase (CAT), and GSH has been reported with the pretreatment of quercetin
*SOD↑,
*MDA↓, quercetin supplementation to layer chickens significantly reduced malondialdehyde (MDA) levels in the kidneys, liver, and heart and increased GSH, CAT, and glutathione peroxidase (GSH-Px) activities in the liver, kidney, and heart tissue
*GPx↑,
*Copper↓, In addition, quercetin can exert antioxidant effects by chelating Cu2+ and Fe2+ in its structure with catechol
*Iron↓,
Apoptosis↓, Quercetin inhibits the proliferation of liver cancer cells via induction of apoptosis and cell cycle arrest [43].
TumCCA↑,
MMP2↓, In HSC-6, SCC-9 human oral cancer cell lines, quercetin inhibits cell viability, migration, and invasion, reduces MMP-2 and MMP-9 abundance, downgrades miR-16, and upgrades HOXA10
MMP9↓,
GlucoseCon↓, quercetin inhibits the mobility of cancer cells by inhibiting glucose uptake and lactic acid production and reducing levels of PKM2, GLUT1, and LDHA, which may have a significant role in controlling breast cancer [56].
lactateProd↓,
PKM2↓,
GLUT1↓,
LDHA↓,
ROS↑, Quercetin encapsulated in solid lipid nanoparticles ,MCF-7 and MCF-10A cells, Increase (ROS)

1748- RosA,    The Role of Rosmarinic Acid in Cancer Prevention and Therapy: Mechanisms of Antioxidant and Anticancer Activity
- Review, Var, NA
AntiCan↑, RA exhibits significant potential as a natural agent for cancer prevention and treatment
*BioAv↝, Various factors, including its lipophilic nature, stability in the gastrointestinal tract, and interactions with food, can significantly influence its absorption
*CardioT↓, RA attenuated these effects by reducing ROS levels, indicating its potential role as a cardioprotective agent during chemotherapy.
*Iron↓, Another significant mechanism antioxidant activity of RA is its capacity to chelate transition metal ions, particularly iron (Fe2+) and copper (Cu2+), which can catalyze the formation of highly reactive hydroxyl radicals through the Fenton reaction.
*ROS↓, forming stable complexes with Fe2+ and Cu2+, thus inhibiting their pro-oxidant activity.
*SOD↑, SOD, CAT, and GPx, play crucial roles in neutralizing ROS and maintaining cellular redox homeostasis. RA upregulates the expression and activity of these enzymes
*Catalase↑,
*GPx↑,
*NRF2↑, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a primary regulator of the antioxidant response
MARK4↓, Anwar’s study demonstrated that RA inhibited MARK4 activity in MDA-MB-231 breast cancer cells, resulting in dose-dependent apoptosis
MMP9↓, RA effectively inhibited cancer cell invasion and migration by reducing matrix metalloproteinase-9 (MMP-9) activity
TumCCA↑, caused cell cycle arrest
Bcl-2↓, RA downregulates Bcl-2 expression and upregulates Bax, thereby promoting apoptosis
BAX↑,
Apoptosis↑,
E-cadherin↑, promoting E-cadherin expression, while downregulating N-cadherin and vimentin
N-cadherin↓,
Vim↓,
Gli1↓, induced apoptosis by downregulating Gli1, a key component of the Hedgehog signaling pathway,
HDAC2↓, RA induced apoptosis by modulating histone deacetylase 2 (HDAC2) expression
Warburg↓, anti-Warburg effect of RA in colorectal carcinoma
Hif1a↓, RA inhibits hypoxia-inducible factor-1 alpha (HIF-1α) and downregulates miR-155
miR-155↓,
p‑PI3K↑, RA has been shown to upregulate p-PI3K, protecting cells through the PI3K/Akt pathway,
ROS↑, RA, induces significant ROS generation in A549 cells, which triggers both apoptosis and autophagy.
*IronCh↑, RA’s dual nature as both a phenolic acid and a flavonoid-related compound enables it to chelate metal ions and prevent the formation of free radicals,

1743- RosA,    New insights into the competition between antioxidant activities and pro-oxidant risks of rosmarinic acid
- Analysis, Var, NA
ROS↑, Finally, the pro-oxidant risk of RA− was also considered via the Fe(iii)-to-Fe(ii) complex reduction process, which may initiate Fenton-like reactions forming reactive HO˙ radicals.
Fenton↑,
eff↑, RA− does not enhance the reduction process when ascorbate anions are present as reducing agents, whereas the pro-oxidant risk becomes remarkable when superoxide anions are found
antiOx↑, The antioxidant activity of RA in this studied system is remarkably higher than that of trolox, ascorbic acid and taxifolin
Iron↓, it is noteworthy that RA− represents strong chelating ability towards both Fe(ii) and Fe(iii) ions compared to its neutral form RA
ROS↑, it is noteworthy that RA− represents strong chelating ability towards both Fe(ii) and Fe(iii) ions compared to its neutral form RA

2201- SK,    Shikonin promotes ferroptosis in HaCaT cells through Nrf2 and alleviates imiquimod-induced psoriasis in mice
- in-vitro, PSA, HaCaT - in-vivo, NA, NA
*eff↑, SHK treatment significantly improved imiquimod (IMQ)-induced psoriasis symptoms in mice
*IL6↓, attenuated the production of inflammatory cytokines, including interleukin (IL)-6, IL-17, and tumor necrosis factor-alpha (i.e., TNF-α)
*IL17↓,
*TNF-α↓,
*lipid-P↑, enhancing intracellular and mitochondrial ferrous and lipid peroxidation levels
*NRF2↓, by regulating expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear receptor coactivator 4 (NCOA4) and glutathione peroxidase 4 (GPX4)
*HO-1↝,
*NCOA4↝,
*GPx4↓, low dose SHK on LPS inhibited GPX4 and Nrf2 expression
*Ferroptosis↓, inhibited ferroptosis in psoriatic skin by reducing inflammation, ameliorating oxidative stress and iron accumulation.
*Inflam↓,
*ROS↓,
*Iron↓,


Showing Research Papers: 1 to 24 of 24

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 24

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   Fenton↑, 2,   Ferroptosis↑, 3,   GPx4↓, 1,   Iron↓, 7,   i-Iron↓, 1,   lipid-P↑, 1,   NRF2↓, 2,   NRF2↑, 1,   ROS↑, 10,  

Metal & Cofactor Biology(tgid=2) ⓘ

TfR1/CD71↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↓, 1,   MPT↑, 1,   mtDam↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 2,   ECAR↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 1,   lactateProd↓, 1,   LDHA↓, 1,   PKM2↓, 1,   PKM2↑, 1,   SLC1A5↓, 1,   Warburg↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 3,   Apoptosis↓, 1,   Apoptosis↑, 4,   BAX↑, 1,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   Casp8↑, 1,   Cyt‑c↑, 1,   DR4↑, 1,   DR5↑, 2,   Fas↑, 1,   Ferroptosis↑, 3,   JNK↑, 2,   p‑MAPK↑, 1,   Pyro↑, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 1,   ER Stress↑, 3,   UPR↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 2,  

DNA Damage & Repair(tgid=10) ⓘ

P53↑, 2,  

Cell Cycle & Senescence(tgid=11) ⓘ

P21↑, 1,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CD44↓, 1,   CSCs↓, 1,   EMT↓, 1,   ERK↑, 1,   Gli1↓, 1,   HDAC2↓, 1,   mTOR↓, 2,   mTOR↑, 1,   Nanog↓, 1,   OCT4↓, 1,   P70S6K↑, 1,   PI3K↓, 1,   p‑PI3K↑, 1,   STAT3↓, 2,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

ATPase↓, 1,   Ca+2↑, 1,   E-cadherin↑, 1,   MARK4↓, 1,   miR-155↓, 1,   MMP2↓, 2,   MMP9↓, 3,   N-cadherin↓, 1,   SOX4↓, 1,   TIMP2↓, 1,   TumCP↓, 2,   Vim↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Barriers & Transport(tgid=15) ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Imm↝, 1,   JAK↓, 1,   M2 MC↓, 1,   MCP1/CCL2↓, 1,   SOCS-3↑, 1,  

Cellular Microenvironment(tgid=17) ⓘ

i-pH↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 4,   eff↑, 5,   MDR1↓, 1,   selectivity↑, 5,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 2,   antiNeop↑, 1,   chemoP↑, 1,  
Total Targets: 91

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

Stroke↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

4-HNE↓, 1,   antiOx↑, 3,   Bil↓, 1,   Catalase↑, 3,   Copper↓, 2,   Fenton↓, 1,   Ferroptosis↓, 5,   GPx↑, 5,   GPx4↓, 1,   GPx4↑, 3,   GSH↑, 4,   GSR↑, 1,   HDL↓, 1,   HO-1↓, 1,   HO-1↑, 1,   HO-1↝, 1,   Iron↓, 13,   i-Iron↓, 3,   lipid-P↓, 2,   lipid-P↑, 1,   MDA↓, 6,   NRF2↓, 1,   NRF2↑, 5,   ROS↓, 13,   SOD↓, 1,   SOD↑, 5,   xCT/SLC7A11↑, 2,  

Metal & Cofactor Biology(tgid=2) ⓘ

Ferritin↑, 1,   FTL↓, 1,   IronCh↑, 4,   NCOA4↝, 1,   TfR1/CD71↓, 2,   Zn2+↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

mtDam↓, 2,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ACSL4↓, 2,   BUN↓, 1,   CREB↑, 1,   LDH↑, 1,   NADPH↓, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↓, 2,   Bax:Bcl2↓, 1,   Casp3↓, 1,   Casp3↑, 1,   Ferroptosis↓, 5,   iNOS↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↓, 1,   other↝, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

ERK↑, 1,   Zn2+↓, 1,  

Migration(tgid=13) ⓘ

Ca+2↝, 1,   PKA↑, 1,   PKCδ?, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

Hif1a↓, 1,   NO↓, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 3,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

IL17↓, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 2,   TNF-α↓, 1,  

Cellular Microenvironment(tgid=17) ⓘ

NOX↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 1,   ADAM10↑, 1,   BDNF↑, 2,   PSD95↑, 2,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1,   BACE/β-secretase↝, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↝, 1,   Dose↝, 1,   eff↑, 2,  

Clinical Biomarkers(tgid=22) ⓘ

Bil↓, 1,   creat↓, 1,   Ferritin↑, 1,   GutMicro↑, 1,   IL6↓, 1,   LDH↑, 1,   Urea↓, 1,  

Functional Outcomes(tgid=23) ⓘ

cardioP↑, 1,   CardioT↓, 1,   cognitive↑, 3,   motorD↑, 1,   neuroP↑, 4,   RenoP↑, 2,   toxicity↓, 2,   toxicity∅, 1,  
Total Targets: 86

Scientific Paper Hit Count for: Iron, Iron
4 Lactoferrin/Talactoferrin
2 Artemisinin
2 Huperzine A/Huperzia serrata
2 IP6 (Inositol 1,2,3,4,5,6-hexakisphosphate)
2 Quercetin
2 Rosmarinic acid
1 Alpha-Lipoic-Acid
1 Carvacrol
1 HydroxyCitric Acid
1 Hyperoside
1 doxorubicin
1 Isoliquiritigenin
1 Kaempferol
1 Licochalcone A
1 Cisplatin
1 Melatonin
1 Myricetin
1 Mung Bean Sprouts
1 Shikonin
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#:160  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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