GPx4 Cancer Research Results

GPx4, Glutathione Peroxidase 4: Click to Expand ⟱
Source:
Type:
GPX4 (Glutathione Peroxidase 4) is a selenoprotein that plays a crucial role in the regulation of ferroptosis, a form of programmed cell death characterized by the iron-dependent accumulation of lipid reactive oxygen species (ROS).
GPX4 has been found to be upregulated in several tumor types, promoting cancer cell survival and resistance to therapy. For instance, GPX4 overexpression has been observed in renal cell carcinoma, pancreatic ductal adenocarcinoma, and triple-negative breast cancer, among others. -GPX4 is known as a lipid peroxidation inhibitor protein, and its antioxidant effect is closely related to ferrous iron
Scientific Papers found: Click to Expand⟱
5458- AF,    Auranofin reveals therapeutic anticancer potential by triggering distinct molecular cell death mechanisms and innate immunity in mutant p53 non-small cell lung cancer
- in-vitro, NSCLC, NA
TrxR↓, Auranofin (AF) is an FDA-approved antirheumatic drug with anticancer properties that acts as a thioredoxin reductase 1 (TrxR) inhibitor.
AntiCan↓,
GPx4↓, Although functionally AF appeared a potent inhibitor of GPX4 in all NCI–H1299 cell lines, the induction of lipid peroxidation and consequently ferroptosis was limited to the p53 R273H expressing cells.
DNAdam↑, AF mainly induced large-scale DNA damage and replication stress, leading to the induction of apoptotic cell death rather than ferroptosis.
toxicity↓, AF is an orally available, lipophilic, organogold compound with a well-known safety profile that was approved by the U.S. Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis (RA).
eff↝, AF represents a potential novel therapeutic strategy to efficiently kill mutant p53 NSCLC tumor cells through distinct immunogenic cell death pathways.

5431- AG,    Advances in research on the anti-tumor mechanism of Astragalus polysaccharides
- Review, Var, NA
AntiTum↑, APS has been increasingly used in cancer therapy owing to its anti-tumor ability as it prevents the progression of prostate, liver, cervical, ovarian, and non-small-cell lung cancer by suppressing tumor cell growth and invasion and enhancing apoptosi
TumCG↓,
TumCI↓,
Apoptosis↑, after APS treatment, the apoptosis of HepG2 cells is accelerated (57).
Imm↑, APS enhances the sensitivity of tumors to antineoplastic agents and improves the body’s immunity
Bcl-2↓, Huang et al. proposed that APS induces H22 (a hepatocellular cancer [HCC] cell line) apoptosis by downregulating Bcl-2 and upregulating Bax expression (56).
BAX↑,
Wnt↓, downregulating the Wnt/β-catenin signaling pathway.
β-catenin/ZEB1↓,
TumCG↓, APS effectively inhibited the growth of MDA-MB-231 (a human breast cancer [BC] cell line) graft tumor (58)
miR-133a-3p↑, apoptosis rate of human osteosarcoma MG63 cells increased owing to the upregulation of miR-133a and inactivation of the JNK signaling pathways (71).
JNK↓,
Fas↑, Li and Shen found that APS can induce apoptosis by activating the Fas death receptor pathway.
P53↑, Zhang et al. showed that APS could activate p53 and p21 and inhibit the expression of Notch1 and Notch3 in vitro, ultimately inhibiting cell proliferation and promoting their apoptosis
P21↑,
NOTCH1↓,
NOTCH3↓,
TumCP↓,
TumCCA↑, Liu et al. found that APS induced the cell cycle of bladder cancer UM-UC-3 to stop in the G0/G1 phase, thus inhibiting its proliferation
GPx4↓, APS was found to reduce GPX4 expression, inhibit the activity of the light chain subunit SLC7A11 (xCT), and promote the formation of BECN1-xCT complex by activating AMPK/BECN1 signaling.
xCT↓,
AMPK↑,
Beclin-1↑,
NF-kB↓, APS could control the proliferation of lung cancer cells (A549 and NCI-H358 cells) by inhibiting the NF-κB signaling pathway (97)
EMT↓, APS treatment led to reduced EMT markers (vimentin, AXL) and MIF levels in cells.
Vim↓,
TumMeta↓, APS inhibits Lewis lung cancer growth and metastasis in mice by significantly reducing VEGF and EGFR expression in cancerous tissues
VEGF↓,
EGFR↓,
eff↑, Nano-drug delivery systems can increase efficiency and reduce toxicity
eff↑, Jiao et al. developed selenium nanoparticles modified with macromolecular weight APS and observed positive results in hepatoma treatment
MMP↓, Subsequent investigations revealed that APS can decrease the ΔΨm values and Bcl-2, p-PI3K, P-gp, and p-AKT levels while elevating Bax expression.
P-gp↓,
MMP9↓, downregulation of MMP-9 expression,
ChemoSen↑, Li et al. observed that APS could enhance the sensitivity of SKOV3 ovarian cancer cells to CDDP treatment by activating the mitochondrial apoptosis pathway and JNK1/2 signaling pathway
SIRT1↓, APS significantly suppressed SIRT1 and SREBP1 expression, decreased cholesterol and triglyceride levels in PC3 and DU145, and attenuated cell proliferation.
SREBP1↓,
TumAuto↑, APS can induce autophagy in colorectal cancer cells by inhibiting the PI3K/AKT/mTOR axis and the development of cancer cells.
PI3K↓,
mTOR↓,
Casp3↑, Shen found that APS elevated caspase-9, caspase-3, and Bax protein levels, decreased Bcl-2 protein expression, and inhibited CD133 and CD44 co-positive colon cancer stem cell proliferation time
Casp9↑,
CD133↓,
CD44↓,
CSCs↓,
QoL↑, QOL was significantly improved as indicated by the reduction in pain and improvement in appetite

5434- AG,    Recent Advances in the Mechanisms and Applications of Astragalus Polysaccharides in Liver Cancer Treatment: An Overview
- Review, Liver, NA
AntiCan↑, Preclinical studies indicate that APS exerts significant anti-liver cancer effects through multiple biological actions, including the promotion of apoptosis, inhibition of proliferation, suppression of epithelial–mesenchymal transition, regulation of
Apoptosis↑,
TumCP↓,
EMT↓,
Imm↑, improving host immune response
ChemoSen↑, APS exhibits synergistic effects when combined with conventional chemotherapeutics and interventional treatments such as transarterial chemoembolisation, improving efficacy and reducing toxicity.
BioAv↓, limitations such as low bioavailability and a lack of large-scale clinical trials remain challenges for clinical translation.
TumCG↓, APS significantly inhibited tumour growth in H22-bearing mice with a dose-dependent effect (100, 200, 400 mg/kg), with the 400 mg/kg group achieving a tumour inhibition rate of 59.01%
IL2↑, APS enhance the thymus and spleen indices and elevates the key cytokines, including IL-2, IL-12, and TNF-α.
IL12↑,
TNF-α↑,
P-gp↓, APS reversed chemoresistance by downregulating P-glycoprotein and MDR1 mRNA expression
MDR1↓,
QoL↑, These effects contributed to improved treatment tolerance and enhanced quality of life [39].
Casp↑, APS can activate both the intrinsic and extrinsic apoptotic pathways, leading to caspase activation and DNA fragmentation
DNAdam↑,
Bcl-2↓, Mechanistically, APS downregulate antiapoptotic proteins such as Bcl-2 while upregulating proapoptotic proteins such as Bax and cleaved caspase-3.
BAX↑,
MMP↓, APS have been shown to disrupt the mitochondrial membrane potential and promote the release of cytochrome c, thereby enhancing apoptotic cascades in hepatocellular carcinoma models.
Cyt‑c↑,
NOTCH1↓, APS (0.1, 0.5, and 1.0 mg/mL) were shown to reduce both mRNA and protein levels of Notch1 in a concentration-dependent manner.
GSK‐3β↓, APS significantly inhibited the proliferation of HepG2 cells by downregulating the expression of glycogen synthase kinase-3β (GSK-3β), with 200 μg/mL being the most effective concentration.
TumCCA↑, APS exerted these effects by inducing cell cycle arrest at the G2/M and S phases, thereby impeding tumour cell proliferation [35].
GSH↓, HepG2 cells. APS also reduced intracellular glutathione (GSH) levels, increased reactive oxygen species (ROS) and lipid peroxidation levels, and elevated intracellular iron ion concentrations—all in a dose-dependent manner.
ROS↑,
lipid-P↑,
c-Iron↑,
GPx4↓, APS treatment led to the downregulation of GPX4 and upregulation of ACSL4, indicating that APS promotes ferroptosis in liver cancer cells.
ACSL4↑,
Ferroptosis↑,
Wnt↓, inhibit the expression of key proteins involved in the Wnt/β-catenin signalling pathway
β-catenin/ZEB1↓,
cycD1/CCND1↓, by downregulating the key oncogenic targets, including β-catenin, C-myc, and cyclin D1, which subsequently reduces Bcl-2 expression and activates the apoptotic cascade in HepG2 liver cancer cells.
Akt↓, It also inhibited the Akt/p-Akt signalling pathway.
PI3K↓, APS inhibit the PI3K/AKT/mTOR signalling pathway, which is a central negative regulator of autophagy.
mTOR↓,
CXCR4↓, PS upregulated the epithelial marker E-cadherin while downregulating the mesenchymal marker vimentin and the chemokine receptor CXCR4 at both mRNA and protein levels, suggesting that APS suppress liver cancer cell growth and metastasis by inhibiting
Vim↓,
PD-L1↓, APS interfere with immune checkpoint signalling by downregulating Programmed death-ligand 1 (PD-L1) expression on tumour cells.
eff↑, The preparation of polysaccharide–SeNP composites typically involves using sodium selenite (Na2SeO3) as the precursor and ascorbic acid (Vc) as the reducing agent, with synthesis carried out via a chemical reduction method in a polysaccharide solutio
eff↑, Mechanistic investigations revealed that AASP–SeNPs elevated intracellular ROS levels and reduced the mitochondrial membrane potential (∆Ψm).
ChemoSen↑, APS enhance doxorubicin-induced endoplasmic reticulum (ER) stress by reducing O-GlcNAcylation levels, thereby promoting apoptosis of liver cancer cells.
ChemoSen↑, APS inhibited BEL-7404 human liver cancer cell growth in a concentration-dependent manner and showed stronger cytotoxicity when combined with cisplatin.
chemoP↑, APS protects against chemotherapy-induced liver injury, particularly that caused by CTX, through antiapoptotic mechanisms

4558- AgNPs,    Role of Oxidative and Nitro-Oxidative Damage in Silver Nanoparticles Cytotoxic Effect against Human Pancreatic Ductal Adenocarcinoma Cells
- in-vitro, PC, PANC1
ROS↑, it is known that AgNPs may induce an accumulation of ROS and alteration of antioxidant systems in different type of tumors, and they are indicated as promising agents for cancer therapy.
selectivity↑, We found that the increase was lower in noncancer cells.
NO↑, PANC-1 cells with 0.5–5 μg/mL of 2.6 nm AgNPs or 5–100 μg/mL of 18 nm AgNPs caused an increase of NO level in a concentration-dependent manner
SOD↓, We observed a significant reduction in cytosolic and mitochondrial SOD and GPX-4 at protein level
GPx4↓,
Catalase↓, we showed that 2.6 nm AgNPs caused a higher decrease in SOD1, SOD2, and CAT at mRNA level after 24 h incubation than 18 nm AgNPs
TumCCA↑, 2.6 nm and 18 nm AgNPs, we noticed a decrease of G0/G1 phase cell population in a concentration-dependent manner compared with control
MMP↓, increase of the percentage of cells with low mitochondrial membrane potential (Δψm), compared to the untreated cells

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↓,

3382- ART/DHA,    Repurposing Artemisinin and its Derivatives as Anticancer Drugs: A Chance or Challenge?
- Review, Var, NA
AntiCan↑, antimalarial drug, artemisinin that has shown anticancer activities in vitro and in vivo.
toxicity↑, safety of artemisinins in long-term cancer therapy requires further investigation.
Ferroptosis↑, Artemisinins acts against cancer cells via various pathways such as inducing apoptosis (Zhu et al., 2014; Zuo et al., 2014) and ferroptosis via the generation of reactive oxygen species (ROS) (Zhu et al., 2021) and causing cell cycle arrest
ROS↑,
TumCCA↑,
BioAv↝, absolute bioavailability was estimated to be 21.6%. ART has good solubility and is not lipophilic
eff↝, ART would not distribute well to the tissues and might be more effective in treating cancers such as leukemia, hepatocellular carcinoma (HCC), or renal cell carcinoma because the liver and kidney are highly perfused organs.
Half-Life↓, Pharmacokinetic studies showed a relatively short t1/2 of artemisinins. For ART, t1/2 was 0.41 h
Ferritin↓, Figure 3
GPx4↓,
NADPH↓,
GSH↓,
BAX↑,
Cyt‑c↑,
cl‑Casp3↑,
VEGF↓, angiogenesis
IL8↓,
COX2↓,
MMP9↓,
E-cadherin↑,
MMP2↓,
NF-kB↓,
p16↑, cell cycle arrest
CDK4↓,
cycD1/CCND1↓,
p62↓, autophagy
LC3II↑,
EMT↓, suppressing EMT and CSCs
CSCs↓,
Wnt↓, Depress Wnt/β-catenin signaling pathway
β-catenin/ZEB1↓,
uPA↓, Inhibit u-PA activity, protein and mRNA expression
TumAuto↑, Emerging evidence suggests that autophagy induction is one of the molecular mechanisms underlying anticancer activity of artemisinins
angioG↓, Inhibition of Angiogenesis
ChemoSen↑, Many studies also reported that the use of artemisinins sensitized cancer cells to conventional chemotherapy and exerted a synergistic effect on apoptosis, inhibition of cell growth, and a reduction of cell viability, leading to a lower IC50 value

3384- ART/DHA,    Dihydroartemisinin triggers ferroptosis in primary liver cancer cells by promoting and unfolded protein response‑induced upregulation of CHAC1 expression
- in-vitro, Liver, Hep3B - in-vitro, Liver, HUH7 - in-vitro, Liver, HepG2
Ferroptosis↑, DHA displayed classic features of ferroptosis, such as increased lipid reactive oxygen species
ROS↑,
GSH↓, decreased activity or expression of glutathione (GSH), glutathione peroxidase 4, solute carrier family (SLC) 7 member 11 and SLC family 3 member 2.
UPR↑, DHA activated all three branches of the UPR
GPx4↓, GSH depletion leads to the suppression of glutathione peroxidase (GPX)4, a key glutathione peroxidase known to catalyze the reduction of lipid ROS
PERK↑, DHA was found to activate PERK/eIF2α/ATF4
eIF2α↑,
ATF4↑,

3387- ART/DHA,    Ferroptosis: A New Research Direction of Artemisinin and Its Derivatives in Anti-Cancer Treatment
- Review, Var, NA
BioAv↓, Artemisinin, extracted from Artemisia annua L., is a poorly water-soluble antimalarial drug
lipid-P↑, promote the accumulation of intracellular lipid peroxides to induce cancer cell ferroptosis, alleviating cancer development and resulting in strong anti-cancer effects in vitro and in vivo.
Ferroptosis↑,
Iron↑, Artemisinin and Its Derivatives Upregulate Fe2+ Levels in Cancer Cells
GPx4↓, GPX4-dependent defense system is significantly inhibited
GSH↓, , leading to a significant decrease in GSH, GPX4, and SLC7A11 protein expression
P53↑, ARTEs can upregulate p53 protein expression in multiple cancer cells
ER Stress↑, ARTEs can trigger ERS in cancer cells to activate the PERK-ATF4 pathway and upregulate GRP78 expression
PERK↑,
ATF4↑,
GRP78/BiP↑,
CHOP↑, which activates CHOP
ROS↑, promoting the accumulation of intracellular ROS, and leading to ferroptosis
NRF2↑, ARTEs can activate the nuclear factor erythroid-derived 2-like 2 (Nrf2) -γ-glutamyl-peptide pathway in cancer cells, resulting in cancer cell ferroptosis resistance

3345- ART/DHA,    Dihydroartemisinin-induced unfolded protein response feedback attenuates ferroptosis via PERK/ATF4/HSPA5 pathway in glioma cells
- in-vitro, GBM, NA
ROS↑, Dihydroartemisinin (DHA) has been shown to exert anticancer activity through iron-dependent reactive oxygen species (ROS) generation, which is similar to ferroptosis, a novel form of cell death
Ferroptosis↑, DHA induced ferroptosis in glioma cells, as characterized by iron-dependent cell death accompanied with ROS generation and lipid peroxidation.
lipid-P↑,
HSP70/HSPA5↑, DHA treatment simultaneously activated a feedback pathway of ferroptosis by increasing the expression of heat shock protein family A (Hsp70) member 5 (HSPA5)
ER Stress↑, DHA caused endoplasmic reticulum (ER) stress in glioma cells, which resulted in the induction of HSPA5 expression by protein kinase R-like ER kinase (PERK)-upregulated activating transcription factor 4 (ATF4)
ATF4↑,
GRP78/BiP↑, HSPA5
MDA↑, DHA significantly increased lipid ROS and MDA levels in glioma cells in a dose- and time-dependent manner.
GSH↓, As an important antioxidant, reduced form GSH was exhausted by DHA
eff↑, Inhibitor of HSPA5 synergistically enhanced anti-tumor effects of DHA
GPx4↑, DHA induced-ER stress in turn activated cell protection against ferroptosis through PERK-ATF4- HSPA5 activation, which promoted the expression of GPX4 to detoxify peroxidized membrane lipids

5378- ART/DHA,    Natural Agents Modulating Ferroptosis in Cancer: Molecular Pathways and Therapeutic Perspectives
- Review, Var, NA
Ferroptosis↑, Artemisinin increases ferroptosis risk in cancer cells by increasing cellular free iron and lipid peroxidation, causing increased membrane permeability and decreased integrity [59]
Iron↑,
lipid-P↑,
MOMP↑,
AntiCan↑, Artemisinin has anticancer and antimalarial properties by upregulating NCOA4 and DMT1 levels, raising ferrous ion levels, and causing ferroptosis by downregulating GSH and GPX4 levels [30, 59, 75].
NCOA4↑,
GSH↓,
GPx4↓,
ROS↑, Artemisinin and its derivatives regulate 20 iron metabolism genes, thereby causing the formation of ROS [76]
ChemoSen↑, Artesunate, when combined with sorafenib, can enhance the susceptibility of hepatocellular carcinoma cells to cisplatin resistance through ferroptosis inhibition [77].
ER Stress↑, artemisinin, specifically ferroptosis, by controlling iron metabolism, producing ROS, and triggering ER‐stress.
DNAdam↑, primary antineoplastic mechanisms of artemisinin are ferroptosis, DNA damage, tumour angiogenesis suppression and cell cycle inhibition [78]
angioG↓,
TumCCA↑,
eff↓, while NAC and ferrostatin‐1 partially reverse these effects [82]

575- ART/DHA,    Dihydroartemisinin initiates ferroptosis in glioblastoma through GPX4 inhibition
- in-vitro, GBM, U87MG
GPx4↓,
xCT∅, constant expression of xCT and ACSL4, suggesting GPX4 was a pivotal target for DHA-activated ferroptosis
ROS↑, lipid ROS levels were increased
Ferroptosis↑,
ACSL4∅,

2575- ART/DHA,  docx,    Artemisia santolinifolia-Mediated Chemosensitization via Activation of Distinct Cell Death Modes and Suppression of STAT3/Survivin-Signaling Pathways in NSCLC
- in-vitro, Lung, H23
ChemoSen↑, Surprisingly, AS synergistically enhanced the cytotoxic effect of DTX by inducing apoptosis in H23 cells through the caspase-dependent pathway, whereas selectively increased necrotic cell population in A549 cells,
GPx4↓, ollowing the decline in GPX4 level and reactive oxygen species (ROS) activation with the highest rate in the combination treatment group
ROS↑,
Ferroptosis↑, predominant contribution of ferroptosis.
eff↑, Our study demonstrated that AS can be a promising chemosensitizer with the combination of conventional chemotherapeutic agent DTX for NSCLC

3173- Ash,    Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma
- in-vitro, neuroblastoma, NA
GPx4↓, WA drops the protein level and activity of GPX4
HO-1↑, WA induces a novel noncanonical ferroptosis pathway by increasing the labile Fe(II) pool upon excessive activation of heme oxygenase 1 (HMOX1) through direct targeting of Kelch-like ECH-associated protein 1 (KEAP1), which is sufficient to induce lipi
lipid-P↑, which is sufficient to induce lipid peroxidation
Keap1↓, In line with this, we observed decreased levels of KEAP1 along with increased levels of NRF2 in conditions in which HMOX1 is upregulated
NRF2↑,
Ferroptosis↑, WA increases intracellular labile Fe(II) upon excessive activation of HMOX1, which is sufficient to induce ferroptosis

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

4822- ASTX,  Rad,    Astaxanthin Synergizes with Ionizing Radiation (IR) in Oral Squamous Cell Carcinoma (OSCC)
tumCV↓, ATX inhibited viability of OSCC cells but not NHOK.
selectivity↑,
RadioS↑, In OSCC cells, ATX further enhanced the cell death induced by IR.
GPx4↓, ATX could synergize with IR, further inhibiting GPX4, SLC7A11 and promoting ACSL4 in OSCC cells.
Ferroptosis↑, ATX might synergize with IR treatment in OSCC partly via ferroptosis.

5501- Ba,    Therapeutic effects and mechanisms of action of Baicalein on stomach cancer: a comprehensive systematic literature review
- Review, GC, NA
AntiCan↑, The review demonstrated that BC exerts therapeutic effects on GC through multiple biochemical mechanisms.
Apoptosis↑, BC plays an important role in inducing apoptosis, inhibiting cell proliferation, and suppressing metastasis in GC cells.
TumCP↓,
TumMeta↓,
BAX↑, graphical abstract
TumAuto↑,
ROS↑,
NRF2↝, BC induced apoptosis and autophagy in MGC-803, SGC-7901, and HGC-27 cells, enhancing cisplatin sensitivity via suppression of the AKT/mTOR pathway and modulation of the Nrf2/Keap1 axis.
PI3K↓,
Akt↓,
NF-kB↓,
TGF-β↓,
SMAD4↓,
GPx4↓, It induces autophagy and ferroptosis, partly through p53 activation and suppression of SLC7A11/GPX4, and disrupts mitochondrial membrane potential via reactive oxygen species (ROS) generation [31, 37]
MMP↓,
*HO-1↑, BC stabilizes Nrf2, leading to the induction of antioxidant enzymes such as HO-1, GST, and NQO1, which mitigate oxidative stress and contribute to its antitumor effects [38].
*GSTs↑,
*antiOx↑,
*AntiTum↑,
*NRF2↑,
ChemoSen↑, BC induced apoptosis and autophagy in MGC-803, SGC-7901, and HGC-27 cells, enhancing cisplatin sensitivity via suppression of the AKT/mTOR pathway and modulation of the Nrf2/Keap1 axis.
Akt↓,
mTOR↓,
FAK↓, reducing FAK expression
Ki-67↓, Immunohistochemical analysis also revealed lower Ki-67 levels, indicating reduced cellular proliferation.

2475- Ba,    Baicalein triggers ferroptosis in colorectal cancer cells via blocking the JAK2/STAT3/GPX4 axis
- in-vitro, CRC, HCT116 - in-vitro, CRC, DLD1 - in-vivo, NA, NA
tumCV↓, We showed that baicalein (1–64 μM) dose-dependently inhibited the viability of human CRC lines HCT116 and DLD1.
GPx4↓, We revealed that baicalein (7.5–30 μM) dose-dependently decreased the expression levels of GPX4, key regulator of ferroptosis, in HCT116 and DLD1
STAT3↓, by blocking janus kinase 2 (JAK2)/STAT3 signaling pathway via direct interaction with JAK2, ultimately leading to ferroptosis in CRC cells.
Ferroptosis↑,

2625- Ba,  LT,    Baicalein and luteolin inhibit ischemia/reperfusion-induced ferroptosis in rat cardiomyocyte
- in-vivo, Stroke, NA
*lipid-P↓, Baicalein and luteolin prevented the Fe-SP-induced lipid peroxidation in rat neonatal cardiomyocytes.
*ACSL4∅, Baicalein and luteolin can reduce the protein levels of ACSL4 and Nrf2, and enhance the protein levels of GPX4 in ischemia/reperfusion-treated rat hearts.
*NRF2∅, Our results suggest that BAI and Lut prevented the I/R-induced increased of ACSL4, NRF2, and HO-1 protein
*GPx4∅, BAI and Lut prevented the I/R-induced increased of ACSL4, NRF2, and HO-1 protein, and the I/R-decreased GPX4 protein levels
*Ferroptosis↓, BAI was found to suppress ferroptosis in cancer cells via reducing reactive oxygen species (ROS) generation.
*ROS↓,
*MDA↓, Moreover, both BAI and Lut decreased ROS and malondialdehyde (MDA) generation and the protein levels of ferroptosis markers, and restored Glutathione peroxidase 4 (GPX4) protein levels in cardiomyocytes reduced by ferroptosis inducers
*eff↑, BAI and Lut reduced the I/R-induced myocardium infarction
*HO-1∅, Our results suggest that BAI and Lut prevented the I/R-induced increased of ACSL4, NRF2, and HO-1 protein

2296- Ba,    The most recent progress of baicalein in its anti-neoplastic effects and mechanisms
- Review, Var, NA
CDK1↓, graphical abstract
Cyc↓,
p27↑,
P21↑,
P53↑,
TumCCA↑, Cell cycle arrest
TumCI↓, Inhibit invastion
MMP2↓,
MMP9↓,
E-cadherin↑,
N-cadherin↓,
Vim↓,
LC3A↑,
p62↓,
p‑mTOR↓,
PD-L1↓,
CAFs/TAFs↓,
VEGF↓,
ROCK1↓,
Bcl-2↓,
Bcl-xL↓,
BAX↑,
ROS↑,
cl‑PARP↑,
Casp3↑,
Casp9↑,
PTEN↑, A549, H460
MMP↓, ↓mitochondrial transmembrane potential, redistribution of cytochrome c,
Cyt‑c↑,
Ca+2↑, ↑Ca2+
PERK↑, ↑PERK, ↑IRE1α, ↑CHOP,
IRE1↑,
CHOP↑,
Copper↑, ↑Cu+2
Snail↓, ↓Snail, ↓vimentin, ↓Twist1,
Vim↓,
Twist↓,
GSH↓, ↑ROS, ↓GSH, ↑MDA, ↓MMP, ↓NRF2, ↓HO-1, ↓GPX4, ↓FTH1, ↑TFR1, ↓p-JAK2, ↓p-STAT3
NRF2↓,
HO-1↓,
GPx4↓,
XIAP↓, ↓Bcl-2, ↓Bcl-xL, ↓XIAP, ↓surviving
survivin↓,
DR5↑, ↑ROS, ↑DR5

2756- BetA,    Betulinic acid inhibits growth of hepatoma cells through activating the NCOA4-mediated ferritinophagy pathway
- in-vitro, HCC, HUH7 - in-vitro, HCC, H1299
TumCP↓, betulinic acid could suppress proliferation and migration of hepatoma cells, raised ROS level and inhibited antioxidation level in cells
ROS↑,
antiOx↓,
TumCG↓, These findings indicate that betulinic acid has the capacity to significantly impede hepatoma cells growth and migration
TumCMig↓,
NRF2↓, The expression of antioxidant proteins Nrf2, GPX4 and HO-1 was also considerably lower in the BETM and BETH groups than in the Control group
GPx4↓,
HO-1↓,
NCOA4↑, suggesting that betulinic acid activates ferritinophagy by boosting NCOA4 expression and FTH1 degradation.
FTH1↓, betulinic acid groups (10 mg/kg, 20 mg/kg, and 40 mg/kg) greatly boosted LC3II and NCOA4 expressions and suppressed FTH1
Ferritin↑, In summation, betulinic acid decreases antioxidation in tumour tissues from nude mice, inhibits ferritin expression, enhances the expression of ferritinophagy-associated protein, activates ferritinophagy, and initiates ferroptosis in tumour cells.
Ferroptosis↑,
GSH↓, In comparison to the Control group, the betulinic acid groups (10 mg/kg, 20 mg/kg and 40 mg/kg) reduced dramatically GSH and hydroxyl radical inhibition capacity in serum, considerably increased serum Fe2+), and decreased dramatically serum MDA
MDA↓,

739- Bor,    Borax regulates iron chaperone- and autophagy-mediated ferroptosis pathway in glioblastoma cells
- in-vitro, GBM, U87MG - in-vitro, Nor, HMC3
TumCG↓,
TumCP↓,
TumCCA↑, remarkably reduced S phase in the U87-MG cells (opposite on normal cells)
PCBP1↓,
GSH↓,
GPx4↓,
Beclin-1↑,
MDA↑,
ACSL4↑,
Casp3↑,
Casp7↑,
Ferroptosis↑,
*toxicity↓, exhibited selectivity by having an opposite effect on normal cells (HMC3).

738- Bor,    Borax induces ferroptosis of glioblastoma by targeting HSPA5/NRF2/GPx4/GSH pathways
- in-vitro, GBM, U251 - in-vitro, GBM, A172 - in-vitro, Nor, SVGp12
TumCP↓,
GPx4↓, borax treatment decreased GPx4, GSH, HSPA5 and NRF2 levels in U251 and A172 cells while increasing MDA levels and caspase‐3/7 activity.
GSH↓,
HSP70/HSPA5↓,
NRF2↓,
MDA↑,
Casp3↑,
Casp7↑,
Ferroptosis↑, Consequently, borax may induce ferroptosis in GBM cells
selectivity↑, Treating SVG cells with borax concentrations ranging from 0 to 800 μM for 24 h did not result in a significant reduction in viability compared to the control group

1447- Bos,    Boswellia carterii n-hexane extract suppresses breast cancer growth via induction of ferroptosis by downregulated GPX4 and upregulated transferrin
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vivo, BC, 4T1 - in-vitro, Nor, MCF10
tumCV↓,
AntiCan↑, BCHE exhibited potent anti-BC activity in vivo
*toxicity↓, no significant toxic effects
Ferroptosis↑,
i-Iron↑, intracellular accumulation of Fe2+
GPx4↓,
ROS↑, upregulation of reactive oxygen species
lipid-P↑, induced lipid peroxidation in BC cells
Tf↑, Transferrin upregulation in tumor-bearing mice
TumCG↓,

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

1410- CUR,    Curcumin induces ferroptosis and apoptosis in osteosarcoma cells by regulating Nrf2/GPX4 signaling pathway
- vitro+vivo, OS, MG63
tumCV↓,
Apoptosis↑,
TumCG↓,
NRF2↓, after treatment with curcumin, Nrf2 and GPX4 levels were significantly decreased
GPx4↓,
HO-1↓,
xCT↓, SLC7A11
ROS↑, our results revealed that after treatment with curcumin, ROS and MDA levels were significantly increased while GSH levels were decreased
MDA↑,
GSH↓,

414- CUR,    Transcriptome Investigation and In Vitro Verification of Curcumin-Induced HO-1 as a Feature of Ferroptosis in Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Ferroptosis↑,
Iron↑,
ROS↑,
lipid-P↑,
MDA↑,
GSH↓,
HO-1↑, Curcumin upregulates a variety of ferroptosis target genes related to redox regulation, especially heme oxygenase-1 (HO-1).
NRF2↑,
GPx↓,
ROS↑,
Iron↑, curcumin caused marked accumulation of intracellular iron
GPx4↓,
HSP70/HSPA5↑,
ATFs↑, ATF4
CHOP↑, DDIT3
MDA↑,
FTL↑, Curcumin upregulated FTL (encoding ferritin light chain), FTH1
FTH1↑,
BACH1↑,
REL↑, v-rel reticuloendotheliosis viral oncogene homolog A
USF1↑,
NFE2L2↑,

448- CUR,    Heat shock protein 27 influences the anti-cancer effect of curcumin in colon cancer cells through ROS production and autophagy activation
- in-vitro, CRC, HT-29
Apoptosis↑,
TumCCA↑, G2/M cell cycle arrest
p‑Akt↓,
Akt↓,
Bcl-2↓,
p‑BAD↓,
BAD↑,
cl‑PARP↑,
ROS↑,
HSP27↑,
Beclin-1↑,
p62↑,
GPx1↓,
GPx4↓,

3215- EGCG,    Epigallocatechin gallate modulates ferroptosis through downregulation of tsRNA-13502 in non-small cell lung cancer
- in-vitro, NSCLC, A549 - in-vitro, NSCLC, H1299
TumCP↓, EGCG resulted in a notable suppression of cell proliferation, as evidenced by a reduction in Ki67 immunofluorescence staining
Ki-67↓,
GPx4↓, EGCG treatment led to a decrease in the expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) while increasing the levels of acyl-CoA synthetase long-chain family member 4 (ACSL4).
ACSL4↑,
Iron↑, accompanied by an increase in intracellular iron, malondialdehyde (MDA), and reactive oxygen species (ROS), alongside ultrastructural alterations characteristic of ferroptosis.
MDA↑,
ROS↑,
Ferroptosis↑,
eff↑, The cooperative effect of metformin and EGCG-activated Nrf2/HO-1 signaling pathway, facilitated by SIRT1-mediated Nrf2 deacetylation, enhances the susceptibility of NSCLC to EGCG modulation by promoting reactive oxygen species (ROS) generation and a
NRF2↑,
HO-1↑,

2204- erastin,    Regulation of ferroptotic cancer cell death by GPX4
- in-vitro, fibroS, HT1080
GSH↓, Erastin Depletes Glutathione to Trigger Selective Ferroptosis
Ferroptosis↑,
ROS↑, erastin induces the formation of ROS, causing an oxidative cell death.
GPx↓, GSH Depletion Inactivates GPX Enzymes to Induce Ferroptosis
GPx4↓, RSL3 Binds to and Inactivates GPX4
lipid-P↑, lipid oxidation is common to both erastin-induced and RSL3-induced ferroptotic cell death
eff↓, Although erastin displayed synthetic lethality in the engineered cells, it did not show selective lethality in RAS-mutated cancer cell lines over RAS wild-type counterparts
eff↑, DLBCLs were more sensitive to erastin than AML and MM cells.

2082- HNK,    Revealing the role of honokiol in human glioma cells by RNA-seq analysis
- in-vitro, GBM, U87MG - in-vitro, GBM, U251
AntiCan↑, In summary, studies have demonstrated that honokiol has multiple anticancer effects
TumCP↑, honokiol suppresses cell proliferation, and promotes autophagy and apoptosis
TumAuto↑,
Apoptosis↑,
*BioAv↑, honokiol could improve bioavailability in nerve tissue through passing the blood-brain barrie
*neuroP↑, honokiol has neuroprotective effects.
*NF-kB↑, honokiol could reduce cytokine production and stimulate glial nuclear factor kappa B (NFκB) to eliminate the inflammatory response during cerebral ischemia-reperfusion activity
MAPK↑, honokiol activated cells MAPK signaling pathway in human glioma cells
GPx4↑, The results showed that the ferroptosis-associated protein GPX4 was suppressed in honokiol-treated cells compared to control cells.
Tf↑, Ferroptosis-associated protein TF was upregulated in both honokiol-treated cell lines compared to the control
BAX↑, BAX was increased, and the expression of Bcl-2 was suppressed in both honokiol-treated cells, indicating that honokiol induced apoptosis in the human glioma cell lines U87-MG and U251-MG.
Bcl-2↓,
antiOx↑, Researchers have found that the antioxidant capacity of honokiol is 1000 times greater than that of vitamin E
Hif1a↓, reduce HIF-1α protein levels and suppress hypoxia-related signaling pathways
Ferroptosis↑, Honokiol activated ferroptosis in human glioma cells

2081- HNK,    Honokiol induces ferroptosis in colon cancer cells by regulating GPX4 activity
- in-vitro, Colon, RKO - in-vitro, Colon, HCT116 - in-vitro, Colon, SW48 - in-vitro, Colon, HT-29 - in-vitro, Colon, LS174T - in-vitro, Colon, HCT8 - in-vitro, Colon, SW480 - in-vivo, NA, NA
tumCV↓, HNK reduced the viability of CC cell lines by increasing ROS and Fe2+ levels
ROS↑, observations suggest that ROS production is a determining factor of HNK cytotoxicity. exact mechanism underlying the pro-oxidant activity of HNK is unclear in CC
Iron↑,
GPx4↓, HNK decreased the activity of Glutathione Peroxidase 4 (GPX4)
mtDam↑, intracellular mitochondria decreased, the membrane density increased, the mitochondrial ridge shrank or disappeared, and the bilayer membrane density increased.
Ferroptosis↑, results suggested that GPX4 may be the key molecule that regulates HNK-induced ferroptosis in CC cells
TumVol↓, tumor volumes and weights were significantly lower in the Lv-NC group than in the Lv-GPX4 group
TumW↓,

2080- HNK,    Honokiol Induces Ferroptosis by Upregulating HMOX1 in Acute Myeloid Leukemia Cells
- in-vitro, AML, THP1 - in-vitro, AML, U937 - in-vitro, AML, SK-HEP-1
tumCV↓, honokiol decreased the viability of the targeted AML cells
TumCCA↑, induced their cell cycle arrest at G0/G1 phase
Ferroptosis↑, Honokiol also triggers a noncanonical ferroptosis pathway in THP-1 and U-937 cells by upregulating the level of intracellular lipid peroxide and HMOX1 significantly.
lipid-P↑,
HO-1↑, HMOX1
GPx4∅, Honokiol elevated the expression of HMOX1 but did not inhibit the expression of GPX4

4641- HT,    Hydroxytyrosol induced ferroptosis through Nrf2 signaling pathway in colorectal cancer cells
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW48
Ferroptosis↑, HT-induced ferroptosis elevates iron levels, lipid peroxidation (LPO) and reactive oxygen species (ROS), while decreasing glutathione (GSH) and mitochondrial membrane potential.
Iron↑,
lipid-P↑, increase in soluble iron pools, which in turn promoted lipid peroxidation
ROS↑,
GSH↓,
MMP↓,
GPx4↓, HT reduced the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) proteins while increasing the expression of Tfr1 protein.
TLR1↑,
eff↓, Additionally, the levels of protein expression of Nrf2 and NQO1 were reversed by two activators of Nrf2, bardoxolone (CDDO) and sulforaphane (SFN)
NRF2↓, HT induces ferroptosis by inhibiting the Nrf2 signaling pathway
ROS↑, Studies have shown that HT not only induces ROS production in tumour cells but also that its antitumor effect may be influenced by its own oxidative properties

1924- JG,    Juglone triggers apoptosis of non-small cell lung cancer through the reactive oxygen species -mediated PI3K/Akt pathway
- in-vitro, Lung, A549
TumCMig↓, substantially suppressed the migration and invasion of these two lung cancer cells
TumCI↓,
TumCCA↑, juglone arrested the cell cycle, induced apoptosis, increased the cleavage of caspase 3
Apoptosis↑,
cl‑Casp3↑,
BAX↑, protein expression of Bax and Cyt c
Cyt‑c↑,
ROS↑, juglone treatment considerably increased intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels
MDA↑,
GPx4↓, suppressed glutathione peroxidase 4 (GPX4) and superoxide dismutase (SOD) activities
SOD↓,
PI3K↓, inhibited the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway
Akt↓,
eff↓, N-acetylcysteine (a ROS scavenger) partially reversed the positive effects of juglone in terms of migration, invasion, ROS production, apoptosis, and PI3K/Akt pathway-associated protein expression

5099- JG,    Juglone induces ferroptosis in glioblastoma cells by inhibiting the Nrf2-GPX4 axis through the phosphorylation of p38MAPK
- vitro+vivo, GBM, LN229 - vitro+vivo, GBM, T98G
Ferroptosis↑, Juglone mainly causes cell death by inducing ferroptosis
p‑MAPK↑, juglone can significantly activate the phosphorylation of p38MAPK
NRF2↓, juglone induces the ferroptosis of GBM by activating the phosphorylation of p38MAPK and negatively regulating the Nrf2-GPX4 signaling pathway.
GPx4↓,
TumPF↓, Juglone significantly inhibits the proliferation of GBM cells and induces cell apoptosis
Apoptosis↑,
ROS↑, Juglone can dose-dependently enhance the accumulation of ROS in GBM cells
GSH↓, juglone can reduce the content of GSH
lipid-P↑, lipid peroxidation
Ki-67↓, The results show that juglone significantly inhibits the expression of Ki67, GPX4, and Nrf2
TumCG↓, juglone inhibits tumor growth in vivo by inducing ferroptosis.

1275- LT,    Mechanism of luteolin induces ferroptosis in nasopharyngeal carcinoma cells
- in-vitro, Laryn, NA
Ferroptosis↑,
MDA↑,
Iron↑,
SOD↓,
GSH↓,
GPx4↓,
SOX4↓,
GDF15↓,

1204- MET,    Metformin induces ferroptosis through the Nrf2/HO-1 signaling in lung cancer
- in-vitro, Lung, A549 - in-vitro, Lung, H1299
MDA↑,
ROS↑,
Iron↑, iron ions
GSH↓,
T-SOD↓,
Catalase↓,
GPx4↓,
xCT↓,
NRF2↓,
HO-1↓,

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

4102- MF,    Modulation of antioxidant enzyme gene expression by extremely low frequency electromagnetic field in post-stroke patients
- Human, Stroke, NA
*Catalase↑, We observed that after ELF-EMF therapy, the mRNA expression of the studied genes (CAT, SOD1, SOD2, GPx1, and GPx4) significantly increased, which enhanced the antioxidant defence of the body.
*SOD1↑,
*SOD2↑,
*GPx1↑,
*GPx4↑,
*Dose↝, 40 Hz frequency at 7 milliTesla, for 15 minutes per day, five days a week, over a four‑week

3457- MF,    Cellular stress response to extremely low‐frequency electromagnetic fields (ELF‐EMF): An explanation for controversial effects of ELF‐EMF on apoptosis
- Review, Var, NA
Apoptosis↑, Ding et al., 8 it was demonstrated that 24‐h exposure to 60 Hz, 5 mT ELF‐EMF could potentiate apoptosis induced by H2O2 in HL‐60 leukaemia cell lines.
H2O2↑,
ROS↑, One of the main mechanisms proposed for defining anticancer effects of ELF‐EMF is induction of apoptosis through upregulation of reactive oxygen species (ROS) which has also been confirmed by different experimental studies.
eff↑, intermittent 100 Hz, 0.7 mT EMF significantly enhanced rate of apoptosis in human hepatoma cell lines pretreated with low‐dose X‐ray radiation.
eff↑, 50 Hz, 45 ± 5 mT pulsed EMF, significantly potentiated rate of apoptosis induced by cyclophosphamide and colchicine
Ca+2↑, Over the past few years, lots of data have shown that ELF‐EMF exposure regulates intracellular Ca2+ level
MAPK↑, Mitogen‐activated protein kinase (MAPK) cascades are among the other important signalling cascades which are stimulated upon exposure to ELF‐EMF in several types of examined cells
*Catalase↑, ELF‐EMF exposure can upregulate expression of different antioxidant target genes including CAT, SOD1, SOD2, GPx1 and GPx4.
*SOD1↑,
*GPx1↑,
*GPx4↑,
*NRF2↑, Activation and upregulation of Nrf2 expression, the master redox‐sensing transcription factor may be the most prominent example in this regard which has been confirmed in a Huntington's disease‐like rat model.
TumAuto↑, Activation of autophagy, ER stress, heat‐shock response and sirtuin 3 expression are among the other identified cellular stress responses to ELF‐EMF exposure
ER Stress↑,
HSPs↑,
SIRT3↑,
ChemoSen↑, Contrarily, when chemotherapy and ELF‐EMF exposure are performed simultaneously, this increase in ROS levels potentiates the oxidative stress induced by chemotherapeutic agents
UPR↑, In consequence of ER stress, cells begin to initiate UPR to counteract stressful condition.
other↑, Since the only proven effects of ELF‐EMF exposure on cells are cellular adaptive responses, ROS overproduction and intracellular calcium overload
PI3K↓, figure 3
JNK↑,
p38↑,
eff↓, ontrarily, when cells are exposed to ELF‐EMF, a new source of ROS production is introduced in cells which can at least partially reverse anticancer effects observed with cell's treatment with melatonin.
*toxicity?, More importantly, ELF‐EMF exposure to normal cells in most cases has shown to be safe and un‐harmful.

582- MF,  immuno,  VitC,    Magnetic field boosted ferroptosis-like cell death and responsive MRI using hybrid vesicles for cancer immunotherapy
- in-vitro, Pca, TRAMP-C1 - in-vivo, NA, NA
Fenton↑, boost, Ascorbic acid (AA, C6H8O6) can act as an electron-donor
Ferroptosis↑, HCSVs and MF efficiently inhibited TRAMP-C1 growth through ferroptosis-mediated cell death.
ROS↑, The generated ferrous ions, inducing stronger Fenton-like oxidation than ferric ions, triggered the higher accumulation of ROS, and finally inhibited tumor cell growth
TumCG↓, Collectively, it was proved that the exogenous magnetic field-boosted Fenton reaction efficiently inhibit tumor growth.
Iron↑, after 10-min MF treatment, the increase of ferrous ions was found in 0.1 h
GPx4↓, combination treatment of MF and HCSVs downregulated GPX4

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

3567- MFrot,  MF,    The Effect of Extremely Low-Frequency Magnetic Field on Stroke Patients: A Systematic Review
- Review, Stroke, NA
*eff↑, All included studies showed a beneficial effect of ELF-MFs on stroke patients
*ROS↓, Improvements were observed in domains such as oxidative stress, inflammation, ischemic lesion size, functional status, depressive symptoms and cognitive abilities.
*Inflam↓,
*cognitive↑, An improvement in cognitive abilities reported in some of the included studies [25,26,27,28] is in line with other researchers’ finding
*Catalase↑, Cichoń et al. [27] also showed that catalase activity in erythrocytes and superoxide dismutase were significantly higher in the experimental group than in the control group.
*SOD↑,
*SOD1↑, similar effect was observed in regard to SOD1 and SOD2 mRNA levels.
*SOD2↑,
*GPx1↑, ELF-MFs impacted also the expression of GPx1 and GPx4 mRNA, which increased in the experimental group about 160% (p < 0.001) and 140% (p < 0.001), respectively.
*GPx4↑,
*IL1β↑, blood samples of IL-1β in the experimental group after 10 sessions of rehabilitation which involved ELF-MFs were significantly higher than in the control group
*neuroP↑, majority of the articles included in this study, a neuroprotective effect of ELF-MFs was indicated
*toxicity∅, Particularly noteworthy is the fact that none of the studies included in this review reported any negative side effects of ELF-MFs.

1273- Myr,    Myricetin Induces Ferroptosis and Inhibits Gastric Cancer Progression by Targeting NOX4
- vitro+vivo, GC, NA
Ferroptosis↑, (iron and ROS are critical for ferroptosis)
MDA↑,
Iron↑,
GSH↓,
NOX4↑, increased NOX4 expression in tumor tissue (is an enzyme that produces reactive oxygen species (ROS), particularly hydrogen peroxide (H₂O₂).)
NRF2↓,
GPx4↓,

4927- PEITC,    Targeting ferroptosis in osteosarcoma
- Review, OS, NA
AntiCan↑, β-Phenethyl isothiocyanate (PEITC) is widely found in cruciferous vegetables and has anti-cancer potential
BioAv↑, great value in OS treatment owing to its unique biological properties such as low clearance and high bioavailability
Ferroptosis↑, mechanism of action is thought to be linked to ferroptosis
TfR1/CD71↑, uplifting the expression of transferrin receptor 1 (TfR1) and elevating the level of reactive iron.
Iron↑,
ROS↑, PEITC induced oxidative stress. Malondialdehyde (MDA) and ROS, products of lipid peroxidation, were raised and GPX4 was diminished to impair intracellular antioxidant defence systems
MDA↑,
lipid-P↑,
GPx4↓,

2958- PL,    Natural product piperlongumine inhibits proliferation of oral squamous carcinoma cells by inducing ferroptosis and inhibiting intracellular antioxidant capacity
- in-vitro, Oral, HSC3
TumCP↓, proliferation rate of PL-treated OSCC cells were decreased in a dose- and time-dependent manner.
lipid-P↑, Lipid peroxidation (LPO) and intracellular reactive oxygen species (ROS) were accumulated after PL treatment.
ROS↑,
DNMT1↑, expression of DMT1 increased, and the expression of FTH1, SLC7A11 and GPX4 decreased.
FTH1↓,
GPx4↓,
eff↓, effect of PL on OSCC cells can be reversed by iron scavengers and antioxidants
GSH↓, PL can inhibit the synthesis of intracellular GSH to induce ferroptosis
Ferroptosis↑,
MDA↓, content of MDA decreased

4965- PSO,  Cisplatin,    The synergistic antitumor effects of psoralidin and cisplatin in gastric cancer by inducing ACSL4-mediated ferroptosis
- vitro+vivo, GC, HGC27 - vitro+vivo, GC, MKN45
TumCP↓, PSO impeded GC cell proliferation, migration, invasion, and growth in vivo.
TumCMig↓,
TumCI↓,
TumCG↓,
*toxicity↓, PSO exhibited no significant toxic effects on organs and mitigated DDP-mediated liver and kidney injuries.
eff↑, The combination of PSO and DDP exhibited enhanced inhibitory functions
Ferroptosis↑, PSO and DDP can significantly promote GC cell ferroptosis.
ACSL4↑, PSO promoted ACSL4 expression and suppressed GPX4, AIFM2, and SLC7A11.
GPx4↓,
ChemoSen↑, PSO may serve as a nontoxic adjuvant to enhance DDP’s efficacy and reduce side effects in GC.
chemoP↑,
AntiTum↑, Moreover, we found that the combination of PSO and DDP had synergistic antitumor effects on GC.
Sepsis↓, PSO has protective effects against sepsis-induced acute lung injury [40] and myocardial injury [41] at a dose of 50 mg/kg.

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

1489- RES,    Molecular mechanisms of resveratrol as chemo and radiosensitizer in cancer
- Review, Var, NA
RadioS↑,
ChemoSen↑,
*BioAv↓, However, in vivo experimental models have demonstrated that RSV is rapidly metabolized and eliminated, which leads to low bioavailability of the compound. 75% of RSV has been shown to be absorbed orally, only 1% is detected in the blood plasma
*BioAv↑, nanocarrier of RSV-loaded poly (ε-caprolactone)-poly (ethylene glycol) nanoparticles with an erythrocyte membrane. This system improved RSV’s poor water solubility
Ferroptosis↑, SV could induce ferroptotic cell death in colorectal cancer by initiating lipid peroxidation and suppressing the expression of SLC7A11 and GPX4
lipid-P↑,
xCT↓,
GPx4↓,
*BioAv↑, Bioactive or bioenhancer compounds have also been used (piperine, quercetin, biflavone ginkgetin) that, in combination with RSV, improve bioavailability, solubility, absorption, and cellular permeability
COX2↓, inhibiting Cyclooxygenase-COX
cycD1/CCND1↓,
FasL↓,
FOXP3↓,
HLA↑,
p‑NF-kB↓, decrease NF-ĸB phosphorylation
BAX↑,
Bcl-2↓,
MALAT1↓, decrease the expression of the lncRNA MALAT1 in colorectal and gastric cancer cells through the Wnt/β-catenin signaling pathway

3023- RosA,    Rosmarinic acid alleviates septic acute respiratory distress syndrome in mice by suppressing the bronchial epithelial RAS-mediated ferroptosis
- in-vivo, Sepsis, NA
*GPx4↑, RA notably inhibited the infiltration into the lungs of neutrophils and monocytes with increased amounts of GPX4 and ACE2 proteins, lung function improvement,
*Inflam↓, decreased inflammatory cytokines levels and ER stress in LPS-induced ARDS in mice.
*ER Stress↓,
*Ferroptosis↓, the anti-ferroptosis effect of RA in LPS-induced septic
*Sepsis↓,
*GRP78/BiP↓, Previously, we reported that RA markedly ameliorated septic-associated mortality and lung injury via inhibiting GRP78/IRE1α/JNK pathway-mediated ERS
*IRE1↓,
JNK↓,


Showing Research Papers: 1 to 50 of 78
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 78

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 1,   Catalase↓, 2,   Copper↑, 1,   Fenton↑, 1,   Ferroptosis↑, 34,   GPx↓, 3,   GPx1↓, 1,   GPx4↓, 40,   GPx4↑, 2,   GPx4∅, 1,   GSH↓, 21,   H2O2↑, 2,   HO-1↓, 4,   HO-1↑, 5,   Iron↓, 1,   Iron↑, 15,   i-Iron↑, 1,   c-Iron↑, 1,   Keap1↓, 1,   lipid-P↑, 15,   MDA↓, 2,   MDA↑, 14,   NADPH/NADP+↓, 1,   NFE2L2↑, 1,   NOX4↑, 1,   NRF2↓, 9,   NRF2↑, 4,   NRF2↝, 1,   ROS↑, 34,   SIRT3↑, 1,   SOD↓, 3,   T-SOD↓, 1,   TrxR↓, 1,   xCT↓, 5,   xCT∅, 1,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 1,   Ferritin↑, 1,   FTH1↓, 3,   FTH1↑, 1,   FTL↑, 1,   NCOA4↑, 3,   Tf↑, 2,   TfR1/CD71↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   MMP↓, 7,   mtDam↑, 2,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACSL4↑, 4,   ACSL4∅, 1,   AMPK↑, 1,   GlucoseCon↓, 1,   Glycolysis↓, 2,   HK2↓, 1,   lactateProd↓, 2,   NADPH↓, 1,   PFKP↓, 1,   Pyruv↓, 1,   SIRT1↓, 1,   SLC1A5↓, 1,   SREBP1↓, 1,   TCA↓, 1,  

Cell Death ⓘ

Akt↓, 7,   p‑Akt↓, 2,   Apoptosis↑, 11,   BAD↑, 1,   p‑BAD↓, 1,   BAX↑, 10,   Bcl-2↓, 7,   Bcl-xL↓, 1,   BIM↑, 1,   Casp↑, 1,   Casp3↑, 5,   cl‑Casp3↑, 2,   Casp7↑, 2,   Casp9↑, 3,   Cyt‑c↑, 5,   DR5↑, 2,   Fas↑, 1,   FasL↓, 1,   Ferroptosis↑, 34,   JNK↓, 2,   JNK↑, 1,   MAPK↑, 3,   p‑MAPK↑, 1,   MOMP↑, 1,   p27↑, 1,   p38↑, 2,   survivin↓, 1,  

Kinase & Signal Transduction ⓘ

CaMKII ↓, 1,   RET↓, 1,  

Transcription & Epigenetics ⓘ

other↑, 1,   tumCV↓, 6,   USF1↑, 1,  

Protein Folding & ER Stress ⓘ

ATFs↑, 1,   CHOP↑, 4,   eIF2α↓, 1,   eIF2α↑, 1,   ER Stress↑, 4,   GRP78/BiP↑, 2,   HSP27↑, 1,   HSP70/HSPA5↓, 1,   HSP70/HSPA5↑, 2,   HSP90↓, 1,   HSPs↑, 1,   IRE1↑, 1,   PERK↑, 3,   UPR↑, 2,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 3,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   LC3A↑, 1,   LC3II↑, 1,   p62↓, 2,   p62↑, 1,   TumAuto↑, 5,  

DNA Damage & Repair ⓘ

DNAdam↑, 3,   DNMT1↑, 1,   p16↑, 1,   P53↑, 3,   cl‑PARP↑, 2,  

Cell Cycle & Senescence ⓘ

CDK1↓, 2,   CDK4↓, 1,   Cyc↓, 1,   cycD1/CCND1↓, 3,   P21↑, 2,   TumCCA↑, 11,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   CD44↓, 2,   cMET↓, 1,   CSCs↓, 3,   EMT↓, 4,   GDF15↓, 1,   GSK‐3β↓, 1,   mTOR↓, 4,   p‑mTOR↓, 2,   Nanog↓, 1,   NOTCH1↓, 3,   NOTCH3↓, 1,   PI3K↓, 6,   PTEN↑, 1,   SOX2↓, 1,   STAT3↓, 2,   TumCG↓, 12,   Wnt↓, 4,  

Migration ⓘ

AP-1↓, 1,   BACH1↑, 1,   Ca+2↓, 1,   Ca+2↑, 2,   CAFs/TAFs↓, 1,   E-cadherin↑, 2,   FAK↓, 1,   HLA↑, 1,   Ki-67↓, 3,   MALAT1↓, 1,   miR-133a-3p↑, 1,   MMP2↓, 2,   MMP9↓, 3,   N-cadherin↓, 1,   PCBP1↓, 1,   ROCK1↓, 1,   SMAD4↓, 1,   Snail↓, 1,   SOX4↓, 1,   TGF-β↓, 1,   TumCI↓, 4,   TumCMig↓, 3,   TumCP↓, 9,   TumCP↑, 1,   TumMeta↓, 3,   TumPF↓, 1,   Twist↓, 1,   uPA↓, 2,   Vim↓, 4,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   ATF4↑, 3,   EGFR↓, 1,   Hif1a↓, 3,   NO↑, 1,   REL↑, 1,   VEGF↓, 3,  

Barriers & Transport ⓘ

GLUT1↓, 1,   P-gp↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   CXCR4↓, 1,   FOXP3↓, 1,   IL12↑, 1,   IL2↑, 1,   IL8↓, 1,   Imm↑, 2,   NF-kB↓, 4,   p‑NF-kB↓, 1,   PD-L1↓, 2,   TLR1↑, 1,   TNF-α↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 1,   BioAv↝, 2,   ChemoSen↑, 12,   eff↓, 8,   eff↑, 11,   eff↝, 2,   Half-Life↓, 1,   MDR1↓, 1,   RadioS↑, 2,   selectivity↑, 3,  

Clinical Biomarkers ⓘ

E6↓, 1,   E7↓, 1,   EGFR↓, 1,   Ferritin↓, 1,   Ferritin↑, 1,   Ki-67↓, 3,   PD-L1↓, 2,  

Functional Outcomes ⓘ

AntiCan↓, 1,   AntiCan↑, 7,   AntiTum↑, 2,   chemoP↑, 2,   QoL↑, 2,   toxicity↓, 1,   toxicity↑, 1,   TumVol↓, 1,   TumW↓, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 223

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 3,   Ferroptosis↓, 2,   GPx1↑, 5,   GPx4↑, 6,   GPx4∅, 1,   GSH↑, 1,   GSTs↑, 1,   HO-1↑, 1,   HO-1∅, 1,   lipid-P↓, 1,   MDA↓, 1,   NRF2↑, 3,   NRF2∅, 1,   OXPHOS↓, 2,   ROS↓, 4,   SOD↑, 2,   SOD1↑, 4,   SOD2↑, 2,  

Mitochondria & Bioenergetics ⓘ

mitResp↓, 1,   MMP↝, 1,  

Core Metabolism/Glycolysis ⓘ

ACSL4∅, 1,   Glycolysis↑, 2,   HK2↑, 2,   PFKL↑, 2,   PFKM↑, 2,   PFKP↑, 1,   PKM2↑, 2,  

Cell Death ⓘ

Ferroptosis↓, 2,  

Transcription & Epigenetics ⓘ

other↝, 1,   tumCV↑, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↓, 1,   GRP78/BiP↓, 1,   IRE1↓, 1,  

Migration ⓘ

TumCMig↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,  

Barriers & Transport ⓘ

GLUT1↑, 2,   GLUT4↑, 1,  

Immune & Inflammatory Signaling ⓘ

IL1β↑, 1,   Inflam↓, 2,   NF-kB↑, 1,  

Cellular Microenvironment ⓘ

pH↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 3,   Dose↝, 1,   eff↑, 2,  

Functional Outcomes ⓘ

AntiTum↑, 1,   cognitive↑, 1,   hepatoP↑, 1,   neuroP↑, 2,   toxicity?, 1,   toxicity↓, 3,   toxicity∅, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 54

Scientific Paper Hit Count for: GPx4, Glutathione Peroxidase 4
9 Shikonin
7 Artemisinin
7 Selenite (Sodium)
6 Magnetic Fields
4 Baicalein
4 Curcumin
3 Honokiol
3 Vitamin C (Ascorbic Acid)
2 Astragalus
2 Ashwagandha(Withaferin A)
2 Radiotherapy/Radiation
2 Luteolin
2 Boron
2 Juglone
2 immunotherapy
2 Rosmarinic acid
2 Thymoquinone
1 Auranofin
1 Silver-NanoParticles
1 Andrographis
1 Docetaxel
1 Astaxanthin
1 Betulinic acid
1 Boswellia (frankincense)
1 Citric Acid
1 EGCG (Epigallocatechin Gallate)
1 erastin
1 HydroxyTyrosol
1 Metformin
1 Magnetic Field Rotating
1 Myricetin
1 Phenethyl isothiocyanate
1 Piperlongumine
1 Psoralidin
1 Cisplatin
1 Quercetin
1 Resveratrol
1 salinomycin
1 Sulfasalazine
1 Selenium
1 Sulforaphane (mainly Broccoli)
1 Silymarin (Milk Thistle) silibinin
1 Salvia miltiorrhiza
1 Aflavin-3,3′-digallate
1 doxorubicin
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#:643  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

Home Page