Ferroptosis Cancer Research Results

Ferroptosis, Ferroptosis: Click to Expand ⟱
Source:
Type: type of cell death
Type of programmed cell death dependent on iron.
Ferroptosis is a form of regulated cell death characterized by the accumulation of lipid peroxides to lethal levels. It is distinct from other forms of cell death, such as apoptosis, necrosis, and autophagy. The process of ferroptosis is heavily dependent on iron metabolism and reactive oxygen species (ROS).
The accumulation of lipid peroxides is a hallmark of ferroptosis. This can occur when the antioxidant defenses, such as glutathione and selenoproteins, are overwhelmed or inhibited. Many cancer cells upregulate GPX4 to evade ferroptosis, making it a potential target for therapy. It has been described that GPX4, xCT and ACSL-4 are the main targets in the regulation of ferroptosis.
Scientific Papers found: Click to Expand⟱
5263- 3BP,  CET,    3-Bromopyruvate overcomes cetuximab resistance in human colorectal cancer cells by inducing autophagy-dependent ferroptosis
- in-vitro, CRC, DLD1 - NA, NA, HCT116
eff↑, Our results demonstrated that the co-treatment of 3-BP and cetuximab synergistically induced an antiproliferative effect in both CRC cell lines
Ferroptosis↓, co-treatment induced ferroptosis, autophagy, and apoptosis.
TumAuto↑,
Apoptosis↑,
FOXO3↑, co-treatment inhibited FOXO3a phosphorylation and degradation and activated the FOXO3a/AMPKα/pBeclin1 and FOXO3a/PUMA pathways, leading to the promotion of ferroptosis, autophagy, and apoptosis in DLD-1
AMPKα↑,
p‑Beclin-1↑,
HK2↓, 3-Bromopyruvate (3-BP), also known as hexokinase II inhibitor II, has shown promise as an anticancer agent against various types of cancer
ATP↓, 3-BP exerts its anticancer effects by manipulating cell energy metabolism and regulating oxidative stress, as evidenced by the accumulation of reactive oxygen species (ROS) [13,14,15,16].
ROS↑,
Dose↝, Eight days postinoculation, xenografted mice were randomly divided into four groups and intraperitoneally injected with PBS, 3-BP, cetuximab, or a combination of 3-BP and cetuximab every four days for five injections.
TumVol↓, 3-BP alone or co-treatment with 3-BP and cetuximab significantly reduced the tumor volume and tumor weight on Day 28, but co-treatment showed a greater reduction than 3-BP alone
TumW↓,
xCT↑, The protein level of SLC7A11 was significantly upregulated in all three cell lines following co-treatment (Fig. 2B).
GSH↓, co-treatment with 3-BP and cetuximab led to glutathione (GSH) depletion (Fig. 2D), reactive oxygen species (ROS) production
eff↓, Knockdown of either ATG5 or Beclin1 attenuated the cell death and MDA production induced by co-treatment
MDA↑,

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

5237- AgNPs,    Nrf2 Activation Mitigates Silver Nanoparticle-Induced Ferroptosis in Hepatocytes
- in-vitro, Liver, HepG2
Ferroptosis↑, we provide evidence that AgNPs trigger ferroptosis in both mouse hepatocytes and HepG2 cells
p62↑, AgNPs increased p62 expression, which in turn stabilized Nrf2 by suppressing its interaction with Keap1.
NRF2↝,
eff↓, Upon activation, Nrf2 enhances the transcription of key antioxidant enzymes, including NQO1 and HO-1, thereby alleviating ferroptosis.

1069- AL,    Allicin promotes autophagy and ferroptosis in esophageal squamous cell carcinoma by activating AMPK/mTOR signaling
- vitro+vivo, ESCC, TE1 - vitro+vivo, ESCC, KYSE-510 - in-vitro, Nor, Het-1A
TumCP↓,
LC3‑Ⅱ/LC3‑Ⅰ↑,
p62↓,
p‑AMPK↑,
mTOR↓,
TumAuto↑,
NCOA4↑,
MDA↑,
Iron↑, elevated malondialdehyde and Fe2+ production levels
TumW↓,
TumVol↓,
ATG5↑,
ATG7↑,
TfR1/CD71↓,
FTH1↓, suppressed the expression of ferritin heavy chain 1 (the major intracellular iron-storage protein)
ROS↑,
Iron↑,
Ferroptosis↑,
*toxicity↓, 80 μg/mL allicin for 24 h did not change the viability of Het-1A cells. A slight reduction in cell viability was observed when Het-1A cells were treated with 160 μg/mL allicin for 24 h

1009- And,  5-FU,    Andrographis-mediated chemosensitization through activation of ferroptosis and suppression of β-catenin/Wnt-signaling pathways in colorectal cancer
- in-vivo, CRC, HCT116 - in-vitro, CRC, SW480
ChemoSen↑, combined treatment
Casp9↑,
Ferroptosis↑, activation of ferroptosis and suppression of β-catenin/Wnt-signaling pathways were the key mediators for the anti-cancer and chemosensitizing effects of andrographis.
Wnt/(β-catenin)↓,
FTL↑,
TP53↑,
ACSL5↑,
GCLC↑,
GCLM↑,
SAT1↑,
STEAP3↑,
ACSL5↑,

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

3390- ART/DHA,    Ferroptosis: The Silver Lining of Cancer Therapy
Ferroptosis↑, Artesunate induces ferroptosis in tumour cells by enhancing lysosomal activity and increasing lysosomal iron concentration
Iron↑,
NCOA4↝, Artesunate regulates ferroptosis by promoting ferritinophagy by regulating the gene expression of NCOA4, which leads to an increase in the iron levels
ROS↑, overproduction of ROS triggered by the Fenton reaction between iron ion and hydrogen peroxide is a crucial factor for inducing ferroptosis.
Fenton↑,
Tf↓, artesunate can induce ferroptosis in Adriamycin-resistant leukaemia cells by decreasing TF levels

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

3395- ART/DHA,    Artesunate Induces Ferroptosis in Hepatic Stellate Cells and Alleviates Liver Fibrosis via the ROCK1/ATF3 Axis
- in-vitro, NA, HSC-T6
*Ferroptosis↑, Art induced ferroptosis in HSCs following glutathione-dependent antioxidant system inactivation resulting from nuclear accumulation of unphosphorylated ATF3 mediated by ROCK1-ubiquitination in vitro
*GSH↓,
*ROCK1↓, Interestingly, the ROCK1 protein level was significantly reduced after Art treatment compared with ROCK2, which raised the probability that ROCK1 was involved in the regulation of ferroptosis in LX2 cells

3396- ART/DHA,    Progress on the study of the anticancer effects of artesunate
- Review, Var, NA
TumCP↓, reported inhibitory effects on cancer cell proliferation, invasion and migration.
TumCI↓,
TumCMig↓,
Apoptosis↑, ART has been reported to induce apoptosis, differentiation and autophagy in colorectal cancer cells by impairing angiogenesis
Diff↑,
TumAuto↑,
angioG↓,
TumCCA↑, inducing cell cycle arrest (11), upregulating ROS levels, regulating signal transduction [for example, activating the AMPK-mTOR-Unc-51-like autophagy activating kinase (ULK1) pathway in human bladder cancer cells]
ROS↑,
AMPK↑,
mTOR↑,
ChemoSen↑, ART has been shown to restore the sensitivity of a number of cancer types to chemotherapeutic drugs by modulating various signaling pathways
Tf↑, ART could upregulate the mRNA levels of transferrin receptor (a positive regulator of ferroptosis), thus inducing apoptosis and ferroptosis in A549 non-small cell lung cancer (NSCLC) cells.
Ferroptosis↑,
Ferritin↓, ferritin degradation, lipid peroxidation and ferroptosis
lipid-P↑,
CDK1↑, Cyclin-dependent kinase 1, 2, 4 and 6
CDK2↑,
CDK4↑,
CDK6↑,
SIRT1↑, Sirt1 levels
COX2↓,
IL1β↓, IL-1? ?
survivin↓, ART can selectively downregulate the expression of survivin and induce the DNA damage response in glial cells to increase cell apoptosis and cell cycle arrest, resulting in increased sensitivity to radiotherapy
DNAdam↑,
RadioS↑,

5381- ART/DHA,    Artemisitene triggers calcium-dependent ferroptosis by disrupting the LSH-EWSR1 interaction in colorectal cancer
- in-vitro, CRC, HCT116 - in-vitro, Nor, NCM460 - in-vitro, CRC, HT29 - in-vitro, CRC, HCT8
Ferroptosis↑, Artemisia annua, acted as a CRC therapeutic agent by promoting calcium-dependent ferroptosis.
CYP24A1↓, ATT repressed cytochrome P450 family 24 subfamily A member 1 (CYP24A1) expression, the pivotal mediator of this response
Ca+2↑, ATT downregulated CYP24A1 expression to elevate calcium levels and induce ferroptosis in CRC cells
SCD1↓, The ensuing calcium overload downregulated stearoyl-CoA desaturase (SCD) by CAMKK2/AMPK/SREBF1 axis, enriching oxidizable fatty acids and sensitizing CRC cells to lethal lipid peroxidation.
FAO↑,
lipid-P↑,
eff↑, The results showed that ATT exhibited the highest cytotoxicity, surpassing that of dihydroartemisinin and artesunate, whereas artemisinin and artemether were only weakly effective
selectivity↑, ATT induced cell death in a strictly time-dependent manner and displayed minimal toxicity toward normal NCM460 epithelial cells
other?, Collectively, these data reveal that ATT-driven calcium overload disrupts fatty-acid homeostasis via SCD inhibition, thereby steering CRC cells toward ferroptosis.

5380- ART/DHA,    Artemisinin and Its Derivatives as Potential Anticancer Agents
- Review, Var, NA
TumCG↓, Artemisinin (1, Figure 2) could suppress cell growth [16], reduce angiogenesis-related factors [17], and induce ferroptosis [18] in breast cancer cell lines
angioG↓,
Ferroptosis↑,
TumCP↑, Dihydroartemisinin (2, Figure 2) exhibited anticancer effects against breast cancer by suppressing cell proliferation [16], inhibiting angiogenesis [19], inducing autophagy [20] and pyroptosis [21], and targeting cancer stem cells (CSCs) [
TumAuto↑,
CSCs↑,
eff↑, Dihydroartemisinin is more potent than artemisinin, as the IC50 values at 24 h were lower on MCF-7 (129.1 μM versus 396.6 μM) and MDA-MB-231 (62.95 μM versus 336.63 μM)
YAP/TEAD↓, Additionally, dihydroartemisinin was proven to have the ability to reduce the expression of yes-associated protein 1 (YAP1), which has been commonly used as a prognostic marker in liver cancer.
TumCCA↑, induced G0/G1 cell cycle arrest and apoptosis by promoting oxygen species (ROS) accumulation.
ROS↑,
ChemoSen↑, The application of combination treatment using artemisinin and its derivatives with commonly used chemotherapy drugs, such as cisplatin, carboplatin, doxorubicin, temozolomide, etc., always exhibits significantly improved anticancer effects
N-cadherin↓, and inhibiting the proliferation, colony formation, and invasiveness of colon cancer cells by inhibiting NRP2, N-cadherin, and Vimentin expression
Vim↓,
MMP9↓, by decreasing the expression of HuR and matrix metalloproteinase (MMP)-9 proteins [24],
eff↑, Further investigations suggested that both dihydroartemisinin treatment and the loss of PRIM2 could lead to a decreased GSH level and induce cellular lipid ROS and mitochondrial MDA expression.
STAT3↓, Recently, artemisinin and its derivatives were reported to have potential as direct STAT3 inhibitors [98].
CD133↓, dihydroartemisinin treatment could significantly reduce the expression of CSC markers (CD133, CD44, Nanog, c-Myc, and OCT4) by downregulating Akt/mTOR pathway
CD44↓,
Nanog↓,
cMyc↓,
OCT4↓,
Akt↓,
mTOR↓,

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]

5377- ART/DHA,    Dihydroartemisinin-induced ferroptosis in acute myeloid leukemia: links to iron metabolism and metallothionein
- in-vitro, AML, NA
AntiCan↑, Artemisinin is an anti-malarial drug that has shown anticancer properties
Ferroptosis↑, Recently, ferroptosis was reported to be induced by dihydroartemisinin (DHA) and linked to iron increase.
Iron↑, We found that treatment of DHA induces early ferroptosis by promoting ferritinophagy and subsequent iron increase.
Mets↑, Furthermore, our study demonstrated that DHA activated zinc metabolism signaling, especially the upregulation of metallothionein (MT).
eff↑, Supportingly, we showed that inhibition MT2A and MT1M isoforms enhanced DHA-induced ferroptosis.
GSH↝, Finally, we demonstrated that DHA-induced ferroptosis alters glutathione pool, which is highly dependent on MTs-driven antioxidant response.
eff↑, DHA cooperates with FAC to increase the intracellular iron pool. ferric citrate iron (FAC)
other↓, Under oxidative stress, MT can release Zn2+ (apo-MT) to form thiol groups and participates in GSSG/ GSH reduction.
eff↑, Our current findings also suggest that MT chemical inhibition can cooperate with DHA in primary AML cells in patients.
other↓, Subsequent MT inhibition may sensitize leukemic cells to lipid peroxidation in vitro by impairing GSH regeneration.

5376- ART/DHA,    Artemisinin compounds sensitize cancer cells to ferroptosis by regulating iron homeostasis
- in-vitro, CRC, HCT116 - in-vitro, CRC, HT29 - in-vitro, CRC, SW48 - in-vitro, BC, MDA-MB-453
Ferroptosis↑, artemisinin compounds can sensitize cancer cells to ferroptosis, a new form of programmed cell death driven by iron-dependent lipid peroxidation.
Ferritin↓, Mechanistically, dihydroartemisinin (DAT) can induce lysosomal degradation of ferritin in an autophagy-independent manner, increasing the cellular free iron level and causing cells to become more sensitive to ferroptosis.
Iron↑,
eff↑, we found that DAT can augment GPX4 inhibition-induced ferroptosis
TumAuto↑, DAT sensitizes cells to ferroptosis by stimulating autophagy.
LC3II↑, it caused an increase of LC3-II production
ROS↑, DAT increases lipid ROS and sensitizes cancer cells to ferroptosis

4991- ART/DHA,  doxoR,    Dihydroartemisinin alleviates doxorubicin-induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy
- in-vivo, Nor, H9c2
*cardioP↑, In vivo, DHA markedly relieved Dox-induced cardiac dysfunction, attenuated oxidative stress, alleviated cardiomyocyte ferroptosis, activated Nrf2, promoted autophagy, and improved the function of lysosomes.
*ROS↓,
*Ferroptosis↓,
*NRF2↑,
Keap1↓, DHA significantly alleviates Dox-induced ferroptosis through the clearance of autophagosomes, including the selective degradation of keap1 and the recovery of lysosomes.

4993- ART/DHA,    Dihydroartemisinin inhibits galectin-1–induced ferroptosis resistance and peritoneal metastasis of gastric cancer via the Nrf2–HO-1 pathway
- vitro+vivo, GC, NA
Ferroptosis↑, DHA suppresses galectin-1-promoted GCPM via the PI3K/Akt/Nrf2/HO-1 pathway in vitro
NRF2↓, DHA promotes ferroptosis by downregulating Nrf2/HO-1
HO-1↓,
PI3K↓, We found that DHA significantly affected galectin-1 expression and inhibited PI3K/Akt activation
Akt↓,
TumMeta↓, DHA inhibits peritoneal metastasis through the PI3K/Akt/Nrf2/HO-1 pathway in vivo

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∅,

556- ART/DHA,    Artemisinins as a novel anti-cancer therapy: Targeting a global cancer pandemic through drug repurposing
- Review, NA, NA
IL6↓,
IL1↓, IL-1β
TNF-α↓,
TGF-β↓, TGF-β1
NF-kB↓,
MIP2↓,
PGE2↓,
NO↓,
Hif1a↓,
KDR/FLK-1↓,
VEGF↓,
MMP2↓,
TIMP2↑,
ITGB1↑,
NCAM↑,
p‑ATM↑,
p‑ATR↑,
p‑CHK1↑,
p‑Chk2↑,
Wnt/(β-catenin)↓,
PI3K↓,
Akt↓,
ERK↓, ERK1/2
cMyc↓,
mTOR↓,
survivin↓,
cMET↓,
EGFR↓,
cycD1/CCND1↓,
cycE1↓,
CDK4/6↓,
p16↑,
p27↑,
Apoptosis↑,
TumAuto↑,
Ferroptosis↑,
oncosis↑,
TumCCA↑, G0/G1 into M phase, G0/G1 into S phase, G1 and G2/M
ROS↑, ovarian cancer cell line model, artesunate induced oxidative stress, DNA double-strand breaks (DSBs) and downregulation of RAD51 foci
DNAdam↑,
RAD51↓,
HR↓,

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.

1026- ART/DHA,    Artemisinin improves the efficiency of anti-PD-L1 therapy in T-cell lymphoma
Ferroptosis↑,
ROS↑,
ERK↓,
PD-L1↓, combination therapy with artemisinin greatly improved the anti-lymphoma effciency of anti-PD-L1 monoclonal antibody.

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

3172- Ash,    Implications of Withaferin A for the metastatic potential and drug resistance in hepatocellular carcinoma cells via Nrf2-mediated EMT and ferroptosis
- in-vitro, HCC, HepG2 - in-vitro, Nor, HL7702
Keap1↑, Notably, Withaferin A elevated Keap1 expression to mitigate Nrf2 signaling activation-mediated epithelial to mesenchymal transition (EMT) and ferroptosis-related protein xCT expression
NRF2↓,
EMT↓, Withaferin A suppresses epithelial-to-mesenchymal transition (EMT) in non-small cell lung cancer
TumCP↓, Withaferin A restrains proliferation, invasion, and VM of hepatoma cells while preserving normal hepatocytes
TumCI↓,
selectivity↑, , treatment with Withaferin A ranging from 1 to 100 μM had little effect on cell viability of human normal liver cells (HL-7702 cells), indicating the little cytotoxicity on normal hepatocytes.
*toxicity↓,
ROS↑, Withaferin A strikingly enhanced ROS () and MDA levels (), but reduced the GSH levels (), indicating the induction of ferroptosis by Withaferin A
MDA↑,
GSH↓,
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

1358- Ash,    Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms
- Review, Var, NA
TumCCA↑,
Apoptosis↑,
TumAuto↑,
Ferroptosis↑,
TumCP↓,
CSCs↓,
TumMeta↓,
EMT↓,
angioG↓,
Vim↓,
HSP90↓,
annexin II↓, annexin II proteins directly bind to WA
m-FAM72A↓,
BCR-ABL↓,
Mortalin↓,
NRF2↓,
cMYB↓,
ROS↑, WA inhibits proliferation through ROS-mediated intrinsic apoptosis
ChemoSen↑, WA and cisplatin, WA produced ROS, while cisplatin caused DNA damage, suggesting that lower doses of cisplatin combined with suboptimal doses of WA could achieve the same effect
eff↑, sulforaphane and WA showed synergistic effects on epigenetic modifiers and cell proliferation in breast cancer cells
ChemoSen↑, WA and sorafenib caused G2/M arrest in anaplastic and papillary thyroid cancer cells
ChemoSen↑, combination of WA and 5-FU executed PERK axis-mediated endoplasmic reticulum (ER) stress-induced autophagy and apoptosis
eff↑, WA and carnosol also exhibit a synergistic effect on pancreatic cancer
*BioAv↓, Saurabh by Saurabh et al and Tianming et al reported oral bioavailability values 1.8% and 32.4 ± 4.8%, respectively, in male rats.
ROCK1↓, In another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angi
TumCI↓,
Sp1/3/4↓, Furthermore, WA exerts potent anti-angiogenic activity in vivo.174 In the Ehrlich ascites tumor model, WA exerts its anti-angiogenic activity by reducing the binding of the transcription factor specificity protein 1 (Sp1) to VEGF
VEGF↓, n another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angio
Hif1a↓, Furthermore, WA suppresses the AK4-HIF-1α signaling axis and acts as a potent antimetastatic agent in lung cancer.Citation79
EGFR↓, WA synergistically inhibited wild-type epidermal growth factor receptor (EGFR) lung cancer cell viability

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.

5452- ATV,    Mevalonate pathway in pancreatic ductal adenocarcinoma: mechanisms driving metabolic and cellular plasticity
- Review, Var, NA
ChemoSen↑, The study further highlighted that statins, which inhibit the mevalonate pathway, could significantly reduce protein glycosylation and enhance chemotherapy sensitivity by suppressing EMT signatures in PDAC organoid models.
HMG-CoA↓,
EMT↓,
Ferroptosis↑, cancer cells upregulate the mevalonate pathway to manage oxidative stress and evade ferroptosis and that inhibiting this pathway, either by statins or fatostatin, an SREBP1 inhibitor, can trigger ferroptotic death.
Hif1a↓, pharmacological inhibition of the mevalonate pathway using statins reduces HIF-1α levels

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

2628- Ba,  Cisplatin,    Baicalein alleviates cisplatin-induced acute kidney injury by inhibiting ALOX12-dependent ferroptosis
- in-vitro, Nor, HK-2
*RenoP↑, Baicalein alleviated cisplatin- and folic acid-induced renal dysfunction and pathological damage and improved cisplatin-induced HK2 cell injury
*12LOX↓, Mechanistically, baicalein reduced the expression of 12-lipoxygenase (ALOX12), which inhibits phospholipid peroxidation and ferroptosis in AKI
*Ferroptosis↓,

2626- Ba,    Molecular targets and therapeutic potential of baicalein: a review
- Review, Var, NA - Review, AD, NA - Review, Stroke, NA
AntiCan↓, anticancer, antidiabetic, antimicrobial, antiaging, neuroprotective, cardioprotective, respiratory protective, gastroprotective, hepatic protective, and renal protective effects
*neuroP↑,
*cardioP↑, Cardioprotective action of baicalein
*hepatoP↑,
*RenoP↑, baicalein’s capacity to lessen cisplatin-induced nephrotoxicity is probably due, at least in part, to the attenuation of renal oxidative and/or nitrative stress
TumCCA↑, Baicalein induces G1/S arrest in lung squamous carcinoma (CH27) cells by downregulating CDK4 and cyclin D1, as well as upregulating cyclin E
CDK4↓,
cycD1/CCND1↓,
cycE/CCNE↑,
BAX↑, SGC-7901 cells showed that when baicalein was administered, Bcl-2 was downregulated and Bax was increased
Bcl-2↓,
VEGF↓, Baicalein inhibits the synthesis of vascular endothelial growth factor (VEGF), HIF-1, c-Myc, and nuclear factor kappa B (NF-κB) in the G1 and S phases of ovarian cancer cell
Hif1a↓,
cMyc↓,
NF-kB↓,
ROS↑, Baicalein produced intracellular reactive oxygen species (ROS) and activated BNIP3 to slow down the development and hasten the apoptosis of MG-63,OS cell
BNIP3↑,
*neuroP↑, Baicalein exhibits neuroprotective qualities against amyloid (AN) functions by preventing AN from aggregating in PC12 neuronal cells to cause A𝛽-induced cytotoxicity
*cognitive↑, baicalein encourages non-amyloidogenic processing of APP, which lowers the generation of A𝛽 and enhances cognitive function
*NO↓, baicalein effectively reduced NO generation and iNOS gene expression
*iNOS↓,
*COX2↓, Baicalein therapy significantly decreased the expression of COX-2 and iNOS, as well as PGE2 and NF-κB, indicating a protective effect against cerebral I/R injury.
*PGE2↓,
*NRF2↑, Baicalein therapy markedly elevated nuclear Nrf2 expression and AMPK phosphorylation in the ischemic cerebral cortex
*p‑AMPK↑,
*Ferroptosis↓, Baicalein suppressed ferroptosis associated with 12/15-LOX, hence lessening the severity of post-traumatic epileptic episodes generated by FeCl3
*lipid-P↓, HT22 cells were damaged by ferroptosis, which is mitigated by baicalein may be due to its lipid peroxidation inhibitor
*ALAT↓, Baicalin lowers the raised levels of hepatic markers alanine transaminase (ALT), aspartate aminotransferase (AST)
*AST↓,
*Fas↓, Baicalin has also been shown to suppress apoptosis, decrease FAS protein expression, block the caspase-8 pathway, and decrease Bax protein production
*BAX↓,
*Apoptosis↓,

2701- BBR,    Berberine Inhibits KLF4 Promoter Methylation and Ferroptosis to Ameliorate Diabetic Nephropathy in Mice
- in-vivo, Diabetic, NA
*Inflam↓, Berberine has various biological activities, including anti-inflammation, antioxidative stress, and antiferroptosis
*antiOx↑,
*Ferroptosis↓,
*RenoP↑, Berberine rescued kidney function and renal structure and prevented renal fibrosis in diabetic nephropathy mice.
*DNMT1↓, Berberine suppressed the expression of DNMT1 and DNMT2 and upregulated KLF4 expression by preventing KLF4 promoter methylation.
*DNMTs↓,
*KLF4↑,

3679- BBR,    Berberine alleviates Alzheimer's disease by activating autophagy and inhibiting ferroptosis through the JNK-p38MAPK signaling pathway
- in-vivo, AD, NA
*Beclin-1↑, autophagy-related markers Beclin1 and LC3B were upregulated and P62 was downregulated after BBR treatment.
*LC3B↑,
*p62↓,
*ROS↓, ROS and lipid peroxide MDA decreased significantly after BBR treatment.
*lipid-P↓,
*MDA↓,
*Ferroptosis↓, expression levels of ferroptosis-related genes TFR1, ASCL4, DMT1, and IREB2 were decreased, while the expression levels of FTH1 and SLC7A11 increased after BBR treatment.
*TfR1/CD71↓,
*FTH1↑,
*memory↑, BBR treatment enhanced spatial memory impairment in 5xFAD mice.
*JNK↓, inhibited ferroptosis by inhibiting the JNK-P38MAPK signaling pathway.
*p38↓,
*Aβ↓, further reducing Aβ plaque deposition, inhibiting inflammatory response,
*Inflam↓,

2757- BetA,    Betulinic Acid Inhibits Glioma Progression by Inducing Ferroptosis Through the PI3K/Akt and NRF2/HO-1 Pathways
- in-vitro, GBM, U251
tumCV↓, BA reduced viability; inhibited colony formation, migration, and invasion; and triggered apoptosis.
TumCMig↓,
TumCI↓,
Apoptosis↑,
p‑PI3K↓, BA administration decreased the levels of phosphorylated PI3K and AKT.
p‑Akt↓,
Ferroptosis↑, BA-induced ferroptosis and HO-1 and NRF2 levels were increased
HO-1↑,
NRF2↑,

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

727- Bor,  RSL3,  erastin,    Enhancement of ferroptosis by boric acid and its potential use as chemosensitizer in anticancer chemotherapy
- in-vitro, Liver, HepG2
ROS↑, at high, pharmacological concentrations
GSH↓, BA can increase intracellular ROS,
TBARS↑,
Ferroptosis↑,
ChemoSen↑, These observations suggest that BA could be exploited as a chemo-sensitizer agent in order to overcome cancer drug resistance in selected conditions.

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↓,

5700- BRU,    Brusatol modulates the Nrf2/GCLC pathway to enhance ferroptosis in the treatment of oral squamous cell carcinoma
- in-vitro, Oral, CAL27
TumCG↓, we found that brusatol (BRT) can effectively inhibit the growth rate of the nude mouse heterotopic transplantation tumor model constructed with Cal-27 cells.
Ferroptosis↑, Secondly, it was proved that brusatol (BRT) can promote the ferroptosis of Cal-27 cells, reduce their survival rate, and inhibit their growth and migration capabilities.
TumCMig↓,
NRF2↓, Nrf2, as a key factor in facilitating ferroptosis by brusatol (BRT),
i-GSH↓, leading to depletion of intracellular GSH, accumulation of Fe2+ and ROS, and the occurrence of ferroptosis in Cal-27 cells.
Iron↑,
ROS↑,

5701- BRU,    Brusatol induced ferroptosis in osteosarcoma cells by modulating the Keap1/Nrf2/SLC7A11 signaling pathway
- in-vitro, OS, NA
TumMeta↓, Brucea javanica and Brucea sumatrana, has been shown to possess the potential to inhibit tumor metastasis and proliferation
TumCP↓,
ROS↑, Bru induced mitochondrial dysfunction and a marked increase in reactive oxygen species in OS cells.
Ferroptosis↑, Bru exerts its anti-OS effects by inducing ferroptosis through the regulation of the Keap1/Nrf2/SLC7A11 signaling pathway.
NRF2↓,
ChemoSen↑, we found that the combination of Bru and the chemotherapeutic agent doxorubicin (DOX) significantly enhanced DOX's anti-OS efficacy by activating apoptotic pathways.

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

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

4770- CoQ10,  VitK2,    Cancer cell stiffening via CoQ10 and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer
- in-vitro, BC, MDA-MB-231
other↑, CoQ10 and UBIAD1 increase membrane fluidity leading to increased cell stiffness in BC
*antiOx↑, CoQ10 (or ubiquinone) is a potent lipid-soluble antioxidant enriched not only in mitochondria but also in plasma membranes
Risk↓, Loss of the CoQ10-biosynthetic enzyme UBIAD1 is associated to a worse prognosis in BC patients.
other↑, Deletion of Ubiad1 gene accelerates BC development in mouse models.
TumMeta↓, UBIAD1 expression limits metastasis formation in aggressive BC lines
ECM/TCF↓, CoQ10 and UBIAD1 expression impairs ECM-mediated signaling and AKT2 pathway in BC cells
Akt2↓,
Ferroptosis↑, UBIAD1 and CoQ10 enhance BC sensitivity to ferroptosis inducers via FSP1
eff↑, While CoQ10 treatment alone does not affect MDA-MB-231 cell viability, the co-treatment with RSL3 significantly enhanced cell death

1600- Cu,    Cu(II) complex that synergistically potentiates cytotoxicity and an antitumor immune response by targeting cellular redox homeostasis
- Review, NA, NA
ER Stress↑, Endoplasmic reticulum stress, mediated by reactive oxygen species (ROS), is thought to induce an antitumor immune response
ROS↑,
AntiTum↑,
GSH↓, Li and coworkers recently reported that copper-cysteine nanoparticles could contribute to both oxidative •OH production and antioxidant GSH depletion
Ferroptosis↑, ferroptosis-dependent ICD response in cancer cells
selectivity↑, Markedly decreased cytotoxicity against the normal cell line, 293T, was seen
GSH/GSSG↓, GSH/GSSH ratio decreased from ∼9.30 to ∼4.71 after treatment with Cu-1 at its IC50 concentration over the course of 12 h
*ROS∅, only a slight increase was observed in (normal) 293T
eff↑, In sharp contrast, Cu-1 demonstrated a greater in vivo antitumor effect compared to oxaliplatin (Fig. 6 B and D) and did not induce systemic toxicity or body weight loss

404- CUR,    Curcumin induces ferroptosis in non-small-cell lung cancer via activating autophagy
- vitro+vivo, Lung, A549 - vitro+vivo, Lung, H1299
TumAuto↑,
TumCG↓,
TumCP↓,
Iron↑, iron overload
GSH↓, GSH depletion
lipid-P↑, accumulation of intracellular iron and lipid‐reactive oxygen species (ROS), lipid peroxidation
GPx↓, GPX4
mtDam↑, mitochondrial membrane rupture
autolysosome↑,
Beclin-1↑,
LC3s↑,
p62↓,
Ferroptosis↑, via activating autophagy


Showing Research Papers: 1 to 50 of 116
Page 1 of 3 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 116

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   Fenton↑, 2,   Ferroptosis↓, 1,   Ferroptosis↑, 42,   GCLC↑, 1,   GCLM↑, 1,   GPx↓, 2,   GPx4↓, 17,   GPx4↑, 1,   GSH↓, 16,   GSH↝, 1,   i-GSH↓, 1,   GSH/GSSG↓, 1,   H2O2↑, 1,   HO-1↓, 2,   HO-1↑, 3,   Iron↑, 12,   i-Iron↓, 1,   i-Iron↑, 1,   c-Iron↑, 1,   Keap1↓, 2,   Keap1↑, 1,   lipid-P↑, 12,   MDA↓, 1,   MDA↑, 8,   Mets↑, 1,   NADPH/NADP+↓, 1,   NRF2↓, 8,   NRF2↑, 4,   NRF2↝, 1,   ROS↑, 32,   TBARS↑, 1,   xCT↓, 1,   xCT↑, 1,   xCT∅, 1,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 3,   Ferritin↑, 1,   FTH1↓, 3,   FTL↑, 1,   NCOA4↑, 4,   NCOA4↝, 1,   STEAP3↑, 1,   Tf↓, 1,   Tf↑, 2,   TfR1/CD71↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 3,   BCR-ABL↓, 1,   MMP↓, 2,   Mortalin↓, 1,   mtDam↑, 2,  

Core Metabolism/Glycolysis ⓘ

ACSL4↑, 2,   ACSL4∅, 1,   ACSL5↑, 2,   AMPK↑, 2,   p‑AMPK↑, 1,   ATG7↑, 1,   cMyc↓, 3,   FAO↑, 1,   GlucoseCon↓, 1,   Glycolysis↓, 2,   HK2↓, 2,   HMG-CoA↓, 1,   lactateProd↓, 2,   MCU↓, 1,   NADPH↓, 1,   PFKP↓, 1,   Pyruv↓, 1,   SAT1↑, 1,   SCD1↓, 1,   SIRT1↑, 1,   TCA↓, 1,  

Cell Death ⓘ

Akt↓, 7,   p‑Akt↓, 2,   Apoptosis↑, 8,   BAX↑, 5,   Bcl-2↓, 4,   BIM↑, 1,   Casp↑, 1,   Casp3↑, 4,   cl‑Casp3↑, 1,   Casp7↑, 2,   Casp9↑, 3,   p‑Chk2↑, 1,   Cyt‑c↑, 3,   DR5↑, 1,   Ferroptosis↓, 1,   Ferroptosis↑, 42,   MAPK↑, 1,   Mcl-1↓, 1,   MOMP↑, 1,   oncosis↑, 1,   p27↑, 1,   p38↑, 1,   survivin↓, 3,   YAP/TEAD↓, 1,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 1,   CaMKII ↓, 1,   RET↓, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

other?, 1,   other↓, 2,   other↑, 2,   tumCV↓, 4,  

Protein Folding & ER Stress ⓘ

CHOP↑, 2,   eIF2α↓, 1,   eIF2α↑, 1,   ER Stress↑, 5,   GRP78/BiP↑, 2,   HSP70/HSPA5↓, 1,   HSP70/HSPA5↑, 1,   HSP90↓, 2,   PERK↑, 2,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   autolysosome↑, 1,   Beclin-1↑, 2,   p‑Beclin-1↑, 1,   BNIP3↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 2,   LC3II↑, 2,   LC3s↑, 1,   p62↓, 3,   p62↑, 1,   TumAuto↑, 10,  

DNA Damage & Repair ⓘ

p‑ATM↑, 1,   p‑ATR↑, 1,   p‑CHK1↑, 1,   DNAdam↑, 4,   m-FAM72A↓, 1,   HR↓, 1,   p16↑, 2,   P53↑, 1,   RAD51↓, 1,   TP53↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK1↑, 1,   CDK2↑, 1,   CDK4↓, 2,   CDK4↑, 1,   cycD1/CCND1↓, 4,   cycE/CCNE↑, 1,   cycE1↓, 1,   TumCCA↑, 10,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   CD44↓, 2,   cMET↓, 2,   cMYB↓, 1,   CSCs↓, 3,   CSCs↑, 1,   Diff↑, 1,   EMT↓, 6,   ERK↓, 2,   FOXO3↑, 1,   GSK‐3β↓, 1,   mTOR↓, 6,   mTOR↑, 2,   p‑mTOR↓, 1,   Nanog↓, 2,   NOTCH1↓, 2,   OCT4↓, 1,   P70S6K↑, 1,   PI3K↓, 4,   p‑PI3K↓, 1,   SOX2↓, 1,   STAT3↓, 3,   TumCG↓, 9,   Wnt↓, 3,   Wnt/(β-catenin)↓, 2,  

Migration ⓘ

Akt2↓, 1,   annexin II↓, 1,   AP-1↓, 1,   Ca+2↓, 2,   Ca+2↑, 1,   CDK4/6↓, 1,   E-cadherin↑, 1,   ITGB1↑, 1,   MMP2↓, 2,   MMP9↓, 2,   N-cadherin↓, 1,   NCAM↑, 1,   PCBP1↓, 1,   ROCK1↓, 1,   TGF-β↓, 1,   TIMP2↑, 1,   TumCI↓, 4,   TumCMig↓, 4,   TumCP↓, 10,   TumCP↑, 1,   TumMeta↓, 5,   uPA↓, 2,   Vim↓, 3,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 5,   ATF4↑, 3,   ECM/TCF↓, 1,   EGFR↓, 2,   Hif1a↓, 7,   KDR/FLK-1↓, 1,   NO↓, 1,   VEGF↓, 4,  

Barriers & Transport ⓘ

GLUT1↓, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   CXCR4↓, 1,   IL1↓, 1,   IL12↑, 1,   IL1β↓, 1,   IL2↑, 1,   IL6↓, 1,   IL8↓, 1,   Imm↑, 1,   MIP2↓, 1,   NF-kB↓, 4,   PD-L1↓, 2,   PGE2↓, 1,   TNF-α↓, 1,   TNF-α↑, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↑, 1,   CYP24A1↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↝, 2,   ChemoSen↑, 17,   Dose↝, 1,   eff↓, 5,   eff↑, 17,   eff↝, 1,   Half-Life↓, 1,   MDR1↓, 1,   RadioS↑, 2,   selectivity↑, 5,  

Clinical Biomarkers ⓘ

E6↓, 1,   E7↓, 1,   EGFR↓, 2,   Ferritin↓, 3,   Ferritin↑, 1,   IL6↓, 1,   PD-L1↓, 2,   TP53↑, 1,  

Functional Outcomes ⓘ

AntiCan↓, 1,   AntiCan↑, 5,   AntiTum↑, 1,   chemoP↑, 1,   QoL↑, 1,   Risk↓, 1,   toxicity↑, 1,   TumVol↓, 2,   TumW↓, 2,  
Total Targets: 247

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Ferroptosis↓, 6,   Ferroptosis↑, 1,   GPx4∅, 1,   GSH↓, 1,   GSH↑, 1,   HO-1∅, 1,   lipid-P↓, 3,   MDA↓, 2,   NRF2↑, 3,   NRF2∅, 1,   ROS↓, 3,   ROS∅, 1,  

Metal & Cofactor Biology ⓘ

FTH1↑, 1,   TfR1/CD71↓, 1,  

Core Metabolism/Glycolysis ⓘ

12LOX↓, 1,   ACSL4∅, 1,   ALAT↓, 1,   p‑AMPK↑, 1,  

Cell Death ⓘ

Apoptosis↓, 1,   BAX↓, 1,   Fas↓, 1,   Ferroptosis↓, 6,   Ferroptosis↑, 1,   iNOS↓, 1,   JNK↓, 1,   p38↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3B↑, 1,   p62↓, 1,  

DNA Damage & Repair ⓘ

DNMT1↓, 1,   DNMTs↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

KLF4↑, 1,  

Migration ⓘ

ROCK1↓, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   Inflam↓, 2,   PGE2↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 2,   cognitive↑, 1,   hepatoP↑, 2,   memory↑, 1,   neuroP↑, 2,   RenoP↑, 3,   toxicity↓, 4,  
Total Targets: 50

Scientific Paper Hit Count for: Ferroptosis, Ferroptosis
19 Artemisinin
8 Shikonin
7 Selenite (Sodium)
6 erastin
4 Ashwagandha(Withaferin A)
4 Baicalein
4 Sulfasalazine
3 Boron
3 Copper and Cu NanoParticles
3 Curcumin
3 Honokiol
3 Piperlongumine
3 Rosmarinic acid
3 salinomycin
2 Andrographis
2 Luteolin
2 Cisplatin
2 Berberine
2 Betulinic acid
2 brusatol
2 Citric Acid
2 Disulfiram
2 Juglone
2 Vitamin C (Ascorbic Acid)
2 Phenethyl isothiocyanate
2 Sulforaphane (mainly Broccoli)
1 3-bromopyruvate
1 cetuximab
1 Astragalus
1 Silver-NanoParticles
1 Allicin (mainly Garlic)
1 5-fluorouracil
1 doxorubicin
1 Docetaxel
1 Astaxanthin
1 Radiotherapy/Radiation
1 Atorvastatin
1 Ras-selective lethal 3
1 Boswellia (frankincense)
1 Coenzyme Q10
1 Vitamin K2
1 diet Methionine-Restricted Diet
1 Dipyridamole
1 EGCG (Epigallocatechin Gallate)
1 Gambogic Acid
1 Hydrogen Gas
1 HydroxyTyrosol
1 Magnetic Fields
1 immunotherapy
1 Myricetin
1 nicotinamide adenine dinucleotide
1 Orlistat
1 Phenylbutyrate
1 Psoralidin
1 Quercetin
1 Resveratrol
1 Selenium
1 Silymarin (Milk Thistle) silibinin
1 Salvia miltiorrhiza
1 Spermidine
1 Osimertinib
1 Adagrasib
1 Aflavin-3,3′-digallate
1 Urolithin
1 Zinc
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#:114  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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