Iron Cancer Research Results

Iron, Iron: Click to Expand ⟱

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Iron is an essential nutrient that is crucial for various cellular processes, including DNA synthesis, cell proliferation, and oxygen transport.
Cancer cells often have increased iron requirements due to their rapid growth and proliferation. Some tumors can acquire iron through various mechanisms, including upregulating iron transport proteins. This can support their growth and survival.
Excess iron can lead to the production of reactive oxygen species (ROS) through Fenton reactions, which can cause oxidative damage to DNA, proteins, and lipids. This oxidative stress can contribute to cancer development and progression.

Scientific Papers found: Click to Expand⟱

5434-

AG,

Recent Advances in the Mechanisms and Applications of Astragalus Polysaccharides in Liver Cancer Treatment: An Overview

Review,

Liver,

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

1069-

AL,

Allicin promotes autophagy and ferroptosis in esophageal squamous cell carcinoma by activating AMPK/mTOR signaling

vitro+vivo,

ESCC,

TE1

10 mg/kg

12.03 μg/mL

mice

vitro+vivo,

ESCC,

KYSE-510

16.76 μg/mL

in-vitro,

Nor,

Het-1A

>160 μg/mL

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

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

33.16 μM

in-vitro,

Lung,

H1650

32.45 μM

TumCG↓,
TumMeta↓,
Ferroptosis↑,
ROS↑,
MDA↑,
Iron↑,
GSH↓, lipid ROS reduced glutathione (GSH) accumulation
GPx4↓,
xCT↓, SLC7A11
MMP↓,
ATP↓,

3387-

ART/DHA,

Ferroptosis: A New Research Direction of Artemisinin and Its Derivatives in Anti-Cancer Treatment

Review,

Var,

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

5379-

ART/DHA,

Iron-fueled ferroptosis: a new axis for immunomodulation to overcome cancer drug resistance—from immune microenvironment crosstalk to therapeutic translation

Ferritin↓, dihydroartemisinin (DAT, which triggers lysosomal ferritin degradation).
Iron↑, DAT has shown promise in reversing carboplatin resistance in ovarian cancer cell lines by expanding the labile iron pool (LIP) and enhancing Fenton reaction-mediated lipid peroxidation (149).
Fenton↑,
lipid-P↑,
ChemoSen↑, Its advantage lies in synergistic effects with conventional chemotherapies, as iron overload amplifies chemotherapy-induced oxidative stress.
ROS↑,
eff↝, However, DAT requires careful monitoring of systemic iron levels to avoid anemia, and its efficacy is reduced in cancer cells with upregulated ferroportin (an iron export protein).

5378-

ART/DHA,

Natural Agents Modulating Ferroptosis in Cancer: Molecular Pathways and Therapeutic Perspectives

Review,

Var,

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,

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

3156-

Ash,

Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug

Review,

Var,

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 Â± 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 2ârelated 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

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

1-100uM BCHE

in-vitro,

BC,

MCF-7

in-vivo,

BC,

4T1

400-800 mg/kg

mouse 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

mouse

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↑,

3700-

Chol,

Eggs and Health Special Issue

Review,

Nor,

*other↑, [1], the components of eggs providing beneficial effects against disease [2,3,4,5,6],
*other↑, the relationship between egg intake and healthy eating index [7]
*Inflam↓, the protective effects of eggs against inflammation [8] and oxidative stress [9].
*ROS↓,
*antiOx↑, antioxidant and anti-inflammatory properties
*Iron↑, egg white protein was very useful for the recovery of iron-deficiency anemia
*cardioP∅, clear that heart disease does not increase by egg intake

1585-

Citrate,

Sodium citrate targeting Ca2+/CAMKK2 pathway exhibits anti-tumor activity through inducing apoptosis and ferroptosis in ovarian cancer

in-vitro,

Ovarian,

SKOV3

15.93 mM

in-vitro,

Ovarian,

A2780S

16.8 mM

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

404-

CUR,

Curcumin induces ferroptosis in non-small-cell lung cancer via activating autophagy

vitro+vivo,

Lung,

A549

mice

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

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

114 μM

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↑,

2821-

CUR,

Antioxidant curcumin induces oxidative stress to kill tumor cells (Review)

Review,

Var,

*antiOx↑, Curcumin is a plant polyphenol in turmeric root and a potent antioxidant
*NRF2↑, regulation by nuclear factor erythroid 2-related factor 2, thereby suppressing reactive oxygen species (ROS) and exerting anti-inflammatory, anti-infective and other pharmacological effects
*ROS↓,
*Inflam↓,
ROS↑, Of note, curcumin induces oxidative stress in tumors. curcumin-induced accumulation of ROS in tumors to kill tumor cells has been noted in several studies
p‑ERK↑, Curcumin promoted ERK/JNK phosphorylation, causing elevated ROS levels and triggering mitochondria-dependent apoptosis
ER Stress↑, Curcumin triggered disturbances in Ca2+ homeostasis, leading to endoplasmic reticulum stress, mitochondrial damage and apoptosis
mtDam↑,
Apoptosis↑,
Akt↓, Curcumin inhibited the AKT/mTOR/p70S6K signaling pathway
mTOR↓,
HO-1↑, Curcumin-induced HO-1 overexpression led to a disturbed intracellular iron distribution and triggered the Fenton reaction
Fenton↑,
GSH↓, Non-small cell lung cancer: Curcumin induced a decrease in GSH and an increase in ROS levels and iron accumulation
Iron↑,
p‑JNK↑, Curcumin causes mitochondrial damage by promoting phosphorylation of ERK and JNK, resulting in the increased release of ROS and cytochrome c into the cytoplasm, thereby triggering a mitochondrion-dependent pathway of apoptosis
Cyt‑c↑,
ATF6↑, thyroid cancer with curcumin, both activating transcription factor (ATF) 6 and the ER stress marker C/EBP homologous protein (CHOP) were activated by curcumin and Ca2+-ATPase activity was also affected.
CHOP↑,

1847-

dietFMD,

VitC,

Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers

in-vitro,

PC,

PANC1

vitamin C (≥0.3 mM)

TumCG↓, Fasting-mimicking diets delay tumor progression
ChemoSen↑, sensitize a wide range of tumors to chemotherapy
eff↑, vitamin C anticancer activity is limited by the up-regulation of the stress-inducible protein heme-oxygenase-1. The fasting-mimicking diet selectivity reverses vitamin C-induced up-regulation of heme-oxygenase-1
HO-1↓, FMD reverses the effect of vitamin C on HO-1(downregulating HO-1)
Ferritin↓,
Iron↑, consequently increasing reactive iron, oxygen species, and cell death
ROS↑, Vitamin C’s pro-oxidant action is strictly dependent on metal-ion redox chemistry. In particular, free iron was shown to be a key player in vitamin C-induced cytotoxic effects
TumCD↑,
IGF-1↓, effects on the insulin-like growth factor 1 (IGF-1)
eff↓, When cancer cells were grown under STS conditions before and during treatment, vitamin C-mediated toxicity was strongly enhanced
eff↓, Conversely, KRAS-wild-type CRC (SW48, HT29), prostate cancer (PC-3), ovarian cancer (COV362) cell lines and a normal colon cell line (CCD841CoN) were resistant to vitamin C when used both as a single agent and in combination with STS

5007-

DSF,

Cu,

Nrf2/HO-1 Alleviates Disulfiram/Copper-Induced Ferroptosis in Oral Squamous Cell Carcinoma

vitro+vivo,

Oral,

AntiTum↑, Accumulating evidence indicates that the disulfiram/copper complex (DSF/Cu) has been shown to have potent antitumor activity against various cancers.
TumCP↓, DSF/Cu reduced the proliferation and clonogenicity of OSCC cells.
Ferroptosis↑, DSF/Cu also induced ferroptosis
Iron↑, Importantly, we confirmed that DSF/Cu could increase the free iron pool, enhance lipid peroxidation, and eventually result in ferroptosis cell death.
lipid-P↑,
NRF2↓, DSF/Cu inhibited the xenograft growth of OSCC cells by suppressing the expression of Nrf2/HO-1.
HO-1↓,

5008-

DSF,

Cu,

Overcoming the compensatory elevation of NRF2 renders hepatocellular carcinoma cells more vulnerable to disulfiram/copper-induced ferroptosis

in-vitro,

HCC,

selectivity↑, We found that DSF/Cu selectively exerted an efficient cytotoxic effect on HCC cell lines, and potently inhibited migration, invasion, and angiogenesis of HCC cells
TumCD↑,
TumCMig↓,
TumCI↓,
angioG↓,
mtDam↑, Importantly, we confirmed that DSF/Cu could intensively impair mitochondrial homeostasis, increase free iron pool, enhance lipid peroxidation, and eventually result in ferroptotic cell death.
Iron↑,
lipid-P↑,
Ferroptosis↑,
NF-kB↑, Of note, a compensatory elevation of NRF2 accompanies the process of ferroptosis, and contributes to the resistance to DSF/Cu.
p‑p62↑, DSF/Cu dramatically activated the phosphorylation of p62, which facilitates competitive binding of Keap1, thus prolonging the half-life of NRF2.
Keap1↓,
eff↑, inhibition of NRF2 expression via RNA interference or pharmacological inhibitors significantly facilitated the accumulation of lipid peroxidation, and rendered HCC cells more sensitive to DSF/Cu induced ferroptosis
eff↓, Conversely, fostering NRF2 expression was capable of ameliorating the cell death activated by DSF/Cu.
ChemoSen↑, Additionally, DSF/Cu could strengthen the cytotoxicity of sorafenib, and arrest tumor growth both in vitro and in vivo, by simultaneously inhibiting the signal pathway of NRF2 and MAPK kinase.

3215-

EGCG,

Epigallocatechin gallate modulates ferroptosis through downregulation of tsRNA-13502 in non-small cell lung cancer

in-vitro,

NSCLC,

A549

 111.1 μM

in-vitro,

NSCLC,

H1299

 5.564 μM

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↑,

2081-

HNK,

Honokiol induces ferroptosis in colon cancer cells by regulating GPX4 activity

in-vitro,

Colon,

RKO

11.42 μM

in-vitro,

Colon,

HCT116

47.65 μM

in-vitro,

Colon,

SW48

in-vitro,

Colon,

HT-29

in-vitro,

Colon,

LS174T

in-vitro,

Colon,

HCT8

in-vitro,

Colon,

SW480

in-vivo,

NA,

mice

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↓,

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

1921-

JG,

Juglone induces ferroptotic effect on hepatocellular carcinoma and pan-cancer via the FOSL1-HMOX1 axis

in-vitro,

PC,

vitro+vivo,

PC,

TumCG↓, Juglone suppressed HCC growth via ferroptosis in vitro and in vivo
Ferroptosis↑,
ROS↑, evidenced by increased levels of iron, lipid peroxidation (LPO), reactive oxygen species (ROS), malondialdehyde (MDA)
Iron↑,
lipid-P↑,
MDA↑,
GSH↓, decreased levels of glutathione (GSH)
FOSL1↑, induce ferroptosis in pan-cancer by activating the FOSL1-HMOX1 axis
HO-1↑, HMOX1

1275-

LT,

Mechanism of luteolin induces ferroptosis in nasopharyngeal carcinoma cells

in-vitro,

Laryn,

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↓,

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

As shown in Fig. 1a, once AA is released under the MF, ferric ions in IONCs are reduced by AA increasing ferrous ions, which are a stronger inducer for Fenton reaction compared with ferric ions

in-vivo,

NA,

TRAMP-C1 tumor-bearing mice

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

1273-

Myr,

Myricetin Induces Ferroptosis and Inhibits Gastric Cancer Progression by Targeting NOX4

vitro+vivo,

GC,

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,

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↓,

4911-

Sal,

MUC1-C is a target of salinomycin in inducing ferroptosis of cancer stem cells

in-vitro,

Var,

DU145

IC50 = 0.45 μM

MUC1-C↓, Our results show that SAL-induced MUC1-C suppression downregulates a MUC1-C→MYC pathway
Ferroptosis↑, SAL as a unique small molecule inhibitor of MUC1-C signaling and demonstrate that MUC1-C is an important effector of resistance to ferroptosis.
CSCs↓, SAL is an effective inhibitor of CSCs
NF-kB↓, SAL suppressed MUC1-C and NF-κB expression in DU-145 and H660 cells
GSR↓, MUC1-C induces GSR expression and GSH production. We found that SAL treatment decreases GSR mRNA and protein levels
GSH↑,
Iron↑, SAL kills CSCs by sequestering iron in lysosomes and inducing ferroptosis

4898-

Sal,

Salinomycin as a potent anticancer stem cell agent: State of the art and future directions

Review,

Var,

EC50 of salinomycin killing CSC‐high GBM cells is around 1.25 μM

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

4904-

Sal,

CUR,

Co-delivery of Salinomycin and Curcumin for Cancer Stem Cell Treatment by Inhibition of Cell Proliferation, Cell Cycle Arrest, and Epithelial–Mesenchymal Transition

CSCs↓, We determined CD44-targeting co-delivery nanoparticles are highly efficacious against BCSCs by inducing G1 cell cycle arrest and limiting epithelial–mesenchymal transition.
TumCCA↑,
EMT↓,
other↝, anti-cancer mechanism of salinomycin is associated with dysregulation of metal ions
TumAuto↑, activation of autophagy-mediated cell death, and inhibition of stem cell maintenance
Iron↑, recent study found that salinomycin and its derivative, ironomycin, exhibited a potent and selective activity against breast cancer stem cells (BCSCs) by accumulating and sequestering iron to induce ferroptosis,
Ferroptosis↑,
BioAv↓, challenging to efficiently deliver salinomycin (Sal) to tumor sites due to its hydrophobicity, unfavorable pharmacokinetic profile, and cytotoxicity during systemic drug administration
ROS↑, Our previous studies showed that conjugation of salinomycin with gold nanoparticles can efficiently induce ferroptotic cell death of BCSCs by increasing the generation of ROS, mitochondrial dysfunction, and lipid oxidation with higher iron accumulati
lipid-P↑,
GPx4↓, and GPX-4 inactivation
eff↑, Salinomycin and curcumin were loaded onto poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles via double emulsion method to form nanoparticles . salinomycin and curcumin showed improved therapeutic efficiency against BCSCs

4906-

Sal,

A Concise Review of Prodigious Salinomycin and Its Derivatives Effective in Treatment of Breast Cancer: (2012–2022)

Review,

BC,

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

5139-

SAS,

Sulfasalazine induces ferroptosis in osteosarcomas by regulating Nrf2/SLC7A11/GPX4 signaling axis

in-vitro,

OS,

MG63

in-vitro,

OS,

U2OS

*Inflam↓, Sulfasalazine (SAS), a commonly used anti-inflammatory drug prescribed for nonspecific gastrointestinal diseases, autoimmune rheumatic diseases, ankylosing spondylitis, and various skin conditions
TumCP↓, Our results demonstrate that SAS significantly inhibited the proliferation and migration of OS cells, inducing apoptosis and effectively attenuating their malignant progression.
TumCMig↓,
Apoptosis↑,
Ferroptosis↑, Notably, SAS-treated OS cells displayed hallmarks of ferroptosis, including iron accumulation, elevated levels of malondialdehyde and reactive oxygen species, and reduced levels of glutathione and superoxide dismutase
Iron↑,
MDA↑,
ROS↑,
GSH↓,
SOD↓,
MMP↓, SAS decreased mitochondrial membrane potential in OS cells, potentially indicating mitochondrial damage during ferroptosis.
NRF2↓, Mechanistically, we found that SAS induced ferroptosis by downregulating the expression of NRF2,
xCT↓, subsequently decreasing the expression of the light chain subunit of the cysteine/glutamate transporter system Xc- (SLC7A11) and glutathione peroxidase 4.
GPx4↓,
FTH1↓, SAS treatment decreased FTH1 protein expression

1483-

SFN,

Targeting p62 by sulforaphane promotes autolysosomal degradation of SLC7A11, inducing ferroptosis for osteosarcoma treatment

in-vitro,

OS,

143B

0-10uM

in-vitro,

Nor,

HEK293

in-vivo,

OS,

25-50mg/kg

subcutaneous tumor-bearing nude mouse model

AntiCan↑, has shown potential anti-cancer effects with negligible toxicity
*toxicity∅, (liver, kidney, heart, spleen, and lung) showed no evidence of toxicity associated with SFN treatment
Ferroptosis↑, results demonstrate the dependency of downregulation of SLC7A11 in SFN-induced ferroptosis in OS cells
ROS↑, elevated ROS levels, lipid peroxidation, and GSH depletion
lipid-P↑,
GSH↓, which was dependent on decreased levels of SLC7A11
p62↑, enhanced p62/SLC7A11 protein-protein interaction, thereby promoting the lysosomal degradation of SLC7A11 and triggering ferroptosis
SLC12A5↓, SFN induces ferroptosis of OS cells through downregulation of SLC7A11
eff↓, ferroptosis inhibitors Fer-1 (ferrostatin-1), DFO (deferoxamine), and Lip-1 (liproxstatin-1) substantially rescued the cells from SFN-induced cell death
GPx4↓, SFN treatment markedly reduced the expression levels of ferroptosis markers GPX4 and SLC7A11 in OS cells
i-Iron↑, validated the intracellular Fe2+ accumulation by SFN
eff↓, SLC7A11 overexpression notably reversed SFN-induced changes in the ROS level, GSH level, and lipid peroxidation
MDA↑, SFN treatment reduced GSH levels and increased MDA production, indicating the induction of ferroptosis
TumVol↓,
TumW↓,
Ki-67↓, subcutaneous tumors revealed significantly lower expression levels of Ki67, SLC7A11, and GPX4, along with upregulated LC3B in the SFN-treated group
LC3B↑,
*Weight∅, no significant difference in body weight was observed between the control and SFN-treated groups

1479-

SFN,

Sulforaphane triggers Sirtuin 3-mediated ferroptosis in colorectal cancer cells via activating the adenosine 5'-monophosphate (AMP)-activated protein kinase/ mechanistic target of rapamycin signaling pathway

in-vitro,

CRC,

HCT116

Ferroptosis↑, sulforaphane triggered the ferroptosis of HCT-116 cells by activating the SIRT3/AMPK/mTOR axis
SIRT3↑,
AMPK↑,
mTOR↑,
tumCV↓, SIRT3 overexpression reduced cell viability and increased intracellular levels of ROS, MDA, and iron
ROS↑,
MDA↑,
Iron↑,

2199-

SK,

Induction of Ferroptosis by Shikonin in Gastric Cancer via the DLEU1/mTOR/GPX4 Axis

in-vitro,

GC,

ROS↑, Shikonin could induce reactive oxygen species (ROS), lipid ROS, intracellular ferrous iron (Fe2+), and malondialdehyde (MDA) in GC.
lipid-P↑,
Iron↑,
MDA↑,
GPx4↓, shikonin decreased the expression of GPX4 by suppressing GPX4 synthesis and decreasing ferritin.
Ferritin↓,
DLEU1↓, shikonin decreased DLEU1 expression in GC cells
mTOR↓, shikonin might decrease GPX4 levels by inhibiting the DLEU1/mTOR pathway.
Ferroptosis↑, shikonin-induced ferroptosis

2198-

SK,

Shikonin suppresses proliferation of osteosarcoma cells by inducing ferroptosis through promoting Nrf2 ubiquitination and inhibiting the xCT/GPX4 regulatory axis

in-vitro,

OS,

MG63

 0.75 uM, 1.5 uM and 3 uM

1.432 uM

in-vitro,

OS,

143B

1.638 uM

TumCP↓, shikonin significantly suppressed OS cells proliferation and blocked the cell cycle progression in vitro.
TumCCA↑,
Ferroptosis↑, ferroptosis in OS cells by promoting the Fe2+ accumulation, reactive oxygen species and lipid peroxidation formation, malondialdehyde production and mitochondrial damage
Iron↑,
ROS↑,
lipid-P↑,
MDA↑,
mtDam↑,
NRF2↓, influenced Nrf2 stability via inducing ubiquitin degradation, which suppressed the expression of Nrf2 downstream targets xCT and GPX4, and led to stimulating ferroptosis. Promoted Nrf2 degradation
xCT↓,
GPx4↓,
GSH/GSSG↓, GSH/GSSG ratio declined after shikonin (1.5 uM) treatment
Keap1↑, shikonin (1.5 uM) significantly downregulated the expression of Nrf2 and upregulated the expression of Keap1

2195-

SK,

Shikonin induces ferroptosis in osteosarcomas through the mitochondrial ROS-regulated HIF-1α/HO-1 axis

in-vitro,

OS,

TumCP↓, At a low dose, Shikonin inhibits OS progression and has a excellent biosafety.
Ferroptosis↓, Shikonin induces ferroptosis in OS cel
Hif1a↑, Shikonin upregualtes HIF-1α/HO-1 axis to produce excess Fe2+ which leads to ROS accumulation on OS cell, followed by ferroptosis.
HO-1↑,
Iron↑,
ROS↑,
GSH/GSSG↓, while simultaneously reducing the GSH/GSSG ratio and GPX4 and SLC7A11 expression
GPx4↓,

2202-

SK,

Enhancing Tumor Therapy of Fe(III)-Shikonin Supramolecular Nanomedicine via Triple Ferroptosis Amplification

in-vitro,

Var,

Iron↑, After delivering into glutathione (GSH)-overexpressed tumor cells, FeShik will disassemble and release Fe2+ to induce cell death via ferroptosis.
Ferroptosis↑,
pH↝, GOx executes its catalytic activity to produce an acid environment and plenty of H2O2 for stimulating •OH generation via the Fenton reaction
H2O2↑,
ROS↑,
Fenton↑,
GSH↓, SRF will suppress the biosynthesis of GSH by inhibiting system Xc-, further deactivating the enzymatic activity of glutathione peroxidase 4 (GPX4).
GPx4↓,
lipid-P↑, Up-regulation of the oxidative stress level and down-regulation of GPX4 expression can dramatically accelerate the accumulation of lethal lipid peroxides, leading to ferroptosis amplification of tumor cells

1284-

SK,

Shikonin induces ferroptosis in multiple myeloma via GOT1-mediated ferritinophagy

in-vitro,

Melanoma,

RPMI-8226

in-vitro,

Melanoma,

U266

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

4892-

Sper,

erastin,

Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer

in-vitro,

Pca,

PC3

in-vivo,

Pca,

Male BALB/c nude mice (5 weeks of age)

Ferroptosis↑, Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe2+ levels in vitro
lipid-P↑,
Iron↑, Strikingly, Spd remarkedly increased the erastin-induced Fe2+ levels, and sustained the Fe2+ levels upon cotreatment
eff↑, Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice.
HO-1↑, heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe2+, is significantly upregulated in response to Spd and erastin cotreatment.
NRF2↑, Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1.
ROS↑, The production of lipid ROS induced by the combination treatment
AntiTum↑, Spd promotes anti-tumor efficacy of erastin in mice
eff↓, The results demonstrated that GSH and NAC completely suppressed ROS production induced by Spd plus erastin, associated with restoration of cell survival

4723-

SSE,

Selenium Induces Ferroptosis in Colorectal Cancer Cells via Direct Interaction with Nrf2 and Gpx4

in-vitro,

CRC,

HCT116

TumCP↓, In vitro experiments using HCT116 cells showed that Na₂SeO₃ treatment inhibited proliferation, increased intracellular Fe2⁺, MDA, and ROS levels, and reduced mitochondrial membrane potential.
Iron↑,
MDA↑,
ROS↑,
MMP↓,
NRF2↓, Western blotting further revealed the downregulation of Nrf2 and Gpx4 proteins upon selenium treatment
GPx4↓,
Ferroptosis↑, Our research findings indicate that sodium selenite may induce ferroptosis by regulating the Nrf2/Gpx4 axis, highlighting its potential as a dual nutrient and pharmacological drug for the treatment of CRC.

5091-

SSE,

Superoxide-mediated ferroptosis in human cancer cells induced by sodium selenite

in-vitro,

GBM,

U87MG

in-vitro,

Cerv,

HeLa

in-vitro,

BC,

MCF-7

in-vitro,

Pca,

PC3

in-vitro,

CRC,

HT-29

in-vitro,

Nor,

SVGp12

Ferroptosis↑, In this study, for the first time, we demonstrate that sodium selenite (SS), a well-established redox-active selenium compound, is a novel inducer of ferroptosis in a variety of human cancer cells.
xCT↓, SS down-regulates ferroptosis regulators; solute carrier family 7 member 11 (SLC7A11), glutathione (GSH), and glutathione peroxidase 4 (GPx4), while it up-regulates iron accumulation and lipid peroxidation (LPO).
GSH↓,
GPx4↓,
Iron↑, SS induces iron accumulation via O2•−-dependent process
lipid-P↑,
ROS↑, SS-induced ferroptotic responses are achieved via ROS, in particular superoxide (O2•−) generation.
eff↓, Antioxidants such as superoxide dismutase (SOD) and Tiron not only scavenged O2•− production, but also markedly rescued SLC7A11 down-regulation, GSH depletion, GPx4 inactivation, iron accumulation, LPO, and ferroptosis.
TumCP↓, SS inhibits the proliferation of human cancer cells
TumCD↑, SS induces non-apoptotic, non-autophagic and non-necroptotic cell death in human cancer cells

5090-

SSE,

Sodium Selenite Induces Ferroptosis in Non-small Cell Lung Cancer A549 Cells Via Reactive Oxygen Species (ROS)/Glutathione (GSH)/Glutathione Peroxidase4 (GPx4) Axis

NA,

Lung,

A549

TumCP↓, sodium selenite could inhibit the proliferation of A549 cells, and the IC50 was 10 10 μmol/L;
ROS↑, sodium selenite could induce ROS accumulation, reduce GSH and MMP levels, increase MDA levels, and downregulate GPX4 expression in A549 cells.
GSH↓,
MMP↓,
GPx4↓,
Iron↑, inducing iron death

5088-

SSE,

Superoxide-mediated ferroptosis in human cancer cells induced by sodium selenite

in-vitro,

BC,

MCF-7

in-vitro,

GBM,

U87MG

in-vitro,

Pca,

PC3

in-vitro,

Cerv,

HeLa

in-vitro,

GBM,

A172

Ferroptosis↑, Sodium selenite selectively induces ferroptosis in multiple human cancer cells.
ROS↑, Superoxide is the ROS molecule responsible for the sodium selenite-induced ferroptosis.
Iron↑, Sodium selenite induces iron accumulation via superoxide dependent mechanism
xCT↓, SS down-regulates ferroptosis regulators; solute carrier family 7 member 11 (SLC7A11), glutathione (GSH), and glutathione peroxidase 4 (GPx4), while it up-regulates iron accumulation and lipid peroxidation (LPO)
GSH↓,
GPx4↓,
lipid-P↑,
TumCP↓, SS inhibits the proliferation of human cancer cells
selectivity↑, Surprisingly, SS had minimal toxicity on SVG P12 cells compared to U87MG human malignant glioma cells

5333-

TFdiG,

Theaflavin-3,3′-Digallate Plays a ROS-Mediated Dual Role in Ferroptosis and Apoptosis via the MAPK Pathway in Human Osteosarcoma Cell Lines and Xenografts

vitro+vivo,

OS,

MG63

tumCV↓, The results showed that TF3 reduced cell viability, suppressed cell proliferation, and caused G0/G1 cell cycle arrest in both MG63 and HOS cell lines in a concentration-dependent manner.
TumCP↓,
TumCCA↑,
Iron↑, TF3 also altered the homeostatic mechanisms for iron storage in the examined cell lines, resulting in an excess of labile iron
ROS↑, Unsurprisingly, TF3 caused oxidative stress through reduced glutathione (GSH) exhaustion, reactive oxygen species (ROS) accumulation, and the Fenton reaction, which triggered ferroptosis and apoptosis in the cells.
GSH↓,
Fenton↑,
Ferroptosis↑,
Apoptosis↑,
MAPK↑, TF3 also induced MAPK signalling pathways, including the ERK, JNK, and p38 MAPK pathways.
ERK↑,
JNK↑,
p38↑,
TumCG↓, TF3 significantly reduced OS growth in the 20 and 40 mg/kg treatment groups but did not significantly affect body weight
Dose↝,
FTH1↓, TF3 downregulated FTH expression in vivo and in vitro to promote the release of Fe2+ and the generation of ROS that are involved in ferroptosis progression
GPx4↓, and downregulated the expression of GPX4, eventually resulting in ferroptosis.

Showing Research Papers: 1 to 47 of 47

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 47

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 2, GSH↑, 1, Iron↑, 1, NRF2↑, 2, ROS↓, 2,

Transcription & Epigenetics ⓘ

other↑, 2,

Immune & Inflammatory Signaling ⓘ

Inflam↓, 3,

Functional Outcomes ⓘ

cardioP∅, 1, hepatoP↑, 1, toxicity↓, 2, toxicity↝, 1, toxicity∅, 1, Weight∅, 1,
Total Targets: 13

Scientific Paper Hit Count for: Iron, Iron

6 Artemisinin
5 Shikonin
4 Curcumin
4 salinomycin
4 Selenite (Sodium)
2 Vitamin C (Ascorbic Acid)
2 Disulfiram
2 Copper and Cu NanoParticles
2 Sulforaphane (mainly Broccoli)
1 Astragalus
1 Allicin (mainly Garlic)
1 Andrographis
1 Ashwagandha(Withaferin A)
1 Boswellia (frankincense)
1 brusatol
1 Choline
1 Citric Acid
1 diet FMD Fasting Mimicking Diet
1 EGCG (Epigallocatechin Gallate)
1 Honokiol
1 HydroxyTyrosol
1 Juglone
1 Luteolin
1 Metformin
1 Magnetic Fields
1 immunotherapy
1 Myricetin
1 Phenethyl isothiocyanate
1 Sulfasalazine
1 Spermidine
1 erastin
1 Aflavin-3,3′-digallate

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:160  State#:%  Dir#:2
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Iron Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Cellular Microenvironment ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Transcription & Epigenetics ⓘ

Immune & Inflammatory Signaling ⓘ

Functional Outcomes ⓘ

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