Fenton Cancer Research Results

Fenton, Fenton Reaction: Click to Expand ⟱
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The Fenton reaction is a chemical reaction that involves the catalytic decomposition of hydrogen peroxide (H2O2) by iron ions (Fe2+ or Fe3+). This reaction produces highly reactive oxygen species (ROS), including hydroxyl radicals (·OH) and superoxide anions (O2·-).
Cancer Progression:
Increased oxidative stress from the Fenton reaction can promote cancer cell proliferation, survival, and metastasis. ROS can activate various signaling pathways that support tumor growth and resistance to apoptosis.
Therapeutic Target:
The Fenton reaction has been explored as a potential therapeutic target. Strategies to manipulate iron levels or enhance the production of ROS in cancer cells are being investigated to selectively induce cell death in tumors.

Formula
Fe2+ + H2O2 → Fe3+ + HO• + OH−
Fe3+ + H2O2 → Fe2+ + HOO• + H+
2 H2O2 → HO• + HOO• + H2O net reaction

– The dysregulation of iron metabolism in certain cancers might serve as a biomarker for targeted treatments that employ Fenton reaction-based strategies.
– Researchers are investigating strategies that harness or amplify the Fenton reaction to selectively kill cancer cells.
- With more available iron, the Fenton reaction can be enhanced, resulting in increased production of hydroxyl radicals. Which can lead to cancer cell death.

See the ROS target for more information
Scientific Papers found: Click to Expand⟱
5977- AgNPs,  CDT,    Silver Nitroprusside as an Efficient Chemodynamic Therapeutic Agent and a Peroxynitrite nanogenerator for Targeted Cancer Therapy
- in-vivo, Ovarian, A2780S - NA, Ovarian, SKOV3
Fenton↑, Chemodynamic therapy (CDT) holds great promise in achieving cancer therapy through Fenton and Fenton-like reactions, which generate highly toxic reactive species
ROS↑, can decompose already existing intracellular H2O2 and produce reactive oxygen species (ROS) to attain a therapeutic outcome.
eff↑, Ag+, Fe2+) based silver pentacyanonitrosylferrate or silver nitroprusside (AgNP) were developed for Fenton like reactions that can specifically kills cancer cells by taking advantage of tumor acidic environment without used of any external stimuli
angioG↓, been reported that Ag-based materials are involved in angiogenesis inhibition by blocking Akt phosphorylation
p‑Akt↓,
EPR↑, These results indicate thatin cancer cell lines internalized AgNP, which partially localized inysosomes and could be relocalized to cytoplasm avoiding degradation due to lysosomal acidic pH, which produce ROS.
selectivity↑, While, in normal fibroblast cells over time AgNP colocalization in lysosomes increased due to the difference in lysosomal pH between cancer and normal cells
selectivity↑, results suggest that AgNP specifically produces ROS in cancer cell lines due to high acidity in comparison to the normal cells.
eff↑, This specific ROS production is probably due to tumor acidic environment in which AgNP act as a Fenton reagent
Cyt‑c↑, Cytochrome c release after AgNP treatment
HO-1↑, In A2780 cell line, HO-1 expression levels increased 8.1-fold when treated with AgNP

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).

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.

5385- AsP,  GoldNP,  GEM,    Development of ascorbyl palmitate based hydrophobic gold nanoparticles as a nanocarrier system for gemcitabine delivery
- in-vitro, BC, NA
ROS↑, At pharmacologic concentrations, ascorbate undergoes oxidation via ascorbate radical, generating cytotoxic hydrogen peroxide (H₂O₂) through Fenton chemistry
Fenton↑,
BioAv↑, Although AsP is more stable than vitamin C, its poor release capacity and water insolubility limit its bioavailability and therapeutic efficacy15,17. Thus, incorporating it into nanoparticle carriers can enhance circulation time and tumor accumulatio
EPR↑, Nanoparticles sized 30–200 nm enhance cell uptake via increased surface area and membrane wrapping, effectively accumulating in tumors

1533- Ba,    Baicalein, as a Prooxidant, Triggers Mitochondrial Apoptosis in MCF-7 Human Breast Cancer Cells Through Mobilization of Intracellular Copper and Reactive Oxygen Species Generation
- in-vitro, BrCC, MCF-7 - in-vitro, Nor, MCF10
tumCV↓,
i-ROS↑, enhancement the level of intracellular ROS exhibit pro-oxidant activity in the presence of copper ions
MMP↓,
Bcl-2↓,
BAX↑,
Cyt‑c↑, release of cytochrome C
Casp9↑,
Casp3↑,
eff↓, The pretreatment with NeoCu (I)-specific chelator) remarkably weakened these effects of baicalein exhibit pro-oxidant activity in the presence of copper ions
selectivity↑, baicalein presented little cytotoxicity to normal breast epithelial cells
*toxicity∅, baicalein presented little cytotoxicity to normal breast epithelial cells. explained by the undetectable levels of copper present in MCF-10A cells.
Apoptosis↑,
Fenton↑, results are in further support that the prooxidant action of baicalein involves the reduction of Cu (II) to Cu (I), and the consequent generation of hydroxyl radicals.

5979- CDT,  AgNPs,    Multifunctional nanomedicines-enabled chemodynamic-synergized multimodal tumor therapy via Fenton and Fenton-like reactions
- Review, Var, NA
Fenton↑, Chemodynamic therapy (CDT) is well-known for using the tumor microenvironment to activate the Fenton reaction or Fenton-like reaction to generate strong oxidative hydroxyl radicals for tumor-specific treatment.
eff↑, High-Z metal nanoparticles include bismuth, hafnium, gold, gadolinium, silver and metal oxide nanoparticles are widely used for enhanced RT/CDT combination therapy

5973- CDT,    Chemodynamic Therapy via Fenton and Fenton-Like Nanomaterials: Strategies and Recent Advances
- Review, Var, NA
Fenton↑, Chemodynamic therapy (CDT), a novel cancer therapeutic strategy defined as the treatment using Fenton or Fenton-like reaction to produce •OH in the tumor region
selectivity↑, CDT has attracted tremendous attention because of its unique advantages: 1) It is tumor-selective with low side effects;
eff↑, CDT has been combined with other therapies like chemotherapy, radiotherapy, phototherapy, sonodynamic therapy, and immunotherapy for achieving enhanced anticancer effects.

5974- CDT,    Chemodynamic nanomaterials for cancer theranostics
- Review, Var, NA
Fenton↑, Fenton- and Fenton-like reaction-based chemodynamic therapy (CDT) are new strategies to enhance anticancer efficacy due to their capacity to generate reactive oxygen species (ROS) and oxygen (O2).
ROS↑,
RadioS↑, the generated O2 can relieve the hypoxic condition in the tumor microenvironment (TME) which hinders efficient photodynamic therapy, radiotherapy, etc.
other↑, due to their high catalytic efficiency and excellent biocompatibility; these include iron-based nanomaterials, other metal-based nanomaterials (including Mn2+, Cu2+, and Mo3+, etc.),
GSH↓, In ferroptosis, the activity of system xc- (SLC7A11) is inhibited, resulting in decreased import of cysteine, GSH depletion, inactivation of the glutathione peroxidase 4 (GPX4), and finally ferroptosis
GPx4↓,
ChemoSen↑, increasingly been recognized as a promising strategy for tumor therapy and have been explored in combination with chemotherapy, PDT, PTT, gas therapy, sonodynamic therapy, radiotherapy, immunotherapy, and magnetic hyperthermia therapy (MHT)
sonoS↑, SDT has many advantages, including deep tissue penetration, controllability, and good patient compliance; however, its therapeutic effect is limited in the hypoxic TME and where there is low ROS release and low sensitivity

2786- CHr,    Chemopreventive and therapeutic potential of chrysin in cancer: mechanistic perspectives
- Review, Var, NA
Apoptosis↑, chrysin inhibits cancer growth through induction of apoptosis, alteration of cell cycle and inhibition of angiogenesis, invasion and metastasis without causing any toxicity and undesirable side effects to normal cells
TumCCA↑,
angioG↓,
TumCI↓,
TumMeta↑,
*toxicity↓,
selectivity↑,
chemoPv↑, Induction of phase II detoxification enzymes, such as glutathione S-transferase (GST) or NAD(P)H:quinone oxidoreductase (QR) is one of the major mechanism of protection against initiation of carcinogenesis
*GSTs↑,
*NADPH↑,
*GSH↑, upregulation of antioxidant and carcinogen detoxification enzymes (glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), GST and QR)
HDAC8↓, inhibits of HDAC8 enzymatic activity
Hif1a↓, Prostate DU145: Inhibits HIF-1a expression through Akt signaling and abrogation of VEGF expression
*ROS↓, chrysin (20 and 40 mg/kg) was shown to exhibit chemopreventive activity by ameliorating oxidative stress and inflammation via NF-kB pathway
*NF-kB↓,
SCF↓, Chrysin has also been reported to have the ability to abolish the stem cell factor (SCF)/c-Kit signaling in human myeloid leukemia cells by preventing the PI3 K pathway
cl‑PARP↑, (PARP) and caspase-3 and concurrently decreasing pro-survival proteins survivin and XIAP
survivin↓,
XIAP↓,
Casp3↑, activation of caspase-3 and -9.
Casp9↑,
GSH↓, chrysin sustains a significant depletion of intracellular GSH concentrations in human NSCLC cells
ChemoSen↑, chrysin potentiates cisplatin toxicity, in part, via synergizing pro-oxidant effects of cisplatin by inducing mitochondrial dysfunction, and by depleting cellular GSH, an important antioxidant defense
Fenton↑, ability to participate in a fenton type chemical reaction
P21↑, upregulation of p21 independent of p53 status and decrease in cyclin D1, CDK2 protein levels
P53↑,
cycD1/CCND1↓,
CDK2↓,
STAT3↓, chrysin inhibits angiogenesis through inhibition of STAT3 and VEGF release mediated by hypoxia through Akt signaling pathway
VEGF↓,
Akt↓,
NRF2↓, Chrysin treatment significantly reduced nrf2 expression in cells at both the mRNA and protein levels through down-regulation of PI3K-Akt and ERK pathways.

1603- Cu,  BP,  SDT,    Glutathione Depletion-Induced ROS/NO Generation for Cascade Breast Cancer Therapy and Enhanced Anti-Tumor Immune Response
- in-vitro, BC, 4T1 - in-vivo, NA, NA
GSH↓, Cu2O was incorporated into BP(black phosphorus) to exhaust the overexpressed intracellular GSH
Fenton↑, However, the Cu+-catalyzed Fenton reaction converts H2O2 into OH at a high reaction rate, even in a neutral environment (160 times than that of Fe2+)
ROS↑, BCL nanoparticles exhibited multifunctional characteristics for GSH depletion-induced ROS/NO generation,
NO↑,
sonoS↑, Numerous studies have confirmed that BP, as a sonosensitizer, can induce ROS generation in cancer therapy
eff↑, These results indicated that an acidic environment can effectively promote Cu release.
NO↑, massive NO production
*toxicity∅, Additionally, no significant body weight loss or apparent histological abnormalities of the major organs (heart, liver, spleen, lungs, and kidneys) were observed, indicating the negligible organ toxicity
eff?, In vivo studies demonstrated that BCL plus US treatment could significantly inhibit tumor growth

1602- Cu,    A simultaneously GSH-depleted bimetallic Cu(ii) complex for enhanced chemodynamic cancer therapy†
- in-vitro, BC, MCF-7 - in-vitro, BC, 4T1 - in-vitro, Lung, A549 - in-vitro, Liver, HepG2
eff↑, enhanced chemodynamic cancer therapy
GSH↓, glutathione (GSH) depletion properties
H2O2↑, overexpressed H2O2
ROS↑, highly cytotoxic hydroxyl radicals (˙OH) that kill cancer cells
*BioAv↑, complex is quickly taken up by cancer cells and distributed in multiple organelles including mitochondria and the nucleus
selectivity↑, toxicity toward normal cells is significantly lower than that toward cancer cells due to the limited expression of H2O2
TumCCA↑, arrest the cell cycle of the G0/G1 phase
Apoptosis↑, inducing apoptosis rather than necrosis
Fenton↑, Cu+-involved reaction can occur with a highest reaction rate (1x10E4 M-1 s-1) in weakly acidic, which is about 160-fold increase over that of Fe2+
*toxicity?, C50 value of CuL-Cuphen to normal cells COS-7 was about 6.3uM.

1571- Cu,    Copper in cancer: From pathogenesis to therapy
- Review, NA, NA
*toxicity↝, The toxicity of Cu overload is known to be due, in part, to the release of ROS via the Fenton or Haber-Weiss reaction, causing lipid, protein, DNA, and RNA damage
ROS↑, Cu-induced ROS can induce lipid peroxidation, which raises hydroxynonenal (HNE) levels and causes lipid peroxidation to become toxic.
lipid-P↓,
HNE↑, raises hydroxynonenal (HNE) levels and causes lipid peroxidation to become toxic
MAPK↑, Cu exposure causes an elevation in intracellular ROS levels, which then stimulates the MAPK signaling pathway, increasing JNK/SAPK and p38 homologous activity and phosphorylation levels
JNK↑, Cu-induced ROS continuously activate JNK, promote the production of the AP-1 transcription factor, increase Beclin 1 and Atg7 production, and cause autophagy and apoptosis in tumor cells
AP-1↑,
Beclin-1↑,
ATG7↑,
TumAuto↑,
Apoptosis↑,
HO-1↑, Fang and colleagues consistently found that Cu activates the ROS/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase-1 (NQO1) signaling cascade to induce autophagy
NQO1↑,
mt-ROS↑, Cu NPs induce complete autophagy by enhancing mitochondrial ROS production and inducing autophagy
Fenton↑, generating large amounts of ROS and oxygen via a Fenton-like reaction

1572- Cu,    Recent Advances in Cancer Therapeutic Copper-Based Nanomaterials for Antitumor Therapy
- Review, NA, NA
eff↑, generate a large number of reactive oxygen species (ROS) when exposed to light, which could be adopted for photodynamic therapy.
Fenton↑, Cu2+ is vulnerable to the reduction to Cu+, allowing Cu to drive the Fenton reaction and produce hydroxyl radicals (·OH).
ROS↑, increasing Cu ions in cancer tissue makes an antitumor impact that mainly involves OS by triggering the Fenton reaction, which can produce ROS
eff↑, compared with other metals (iron, chromium, cobalt and nickel), the Cu-based Fenton reaction can react in wider pH range
mtDam↑, Excessive Cu can induce the toxic level of ROS that may aggravate the mitochondrial ROS, causing mitochondrial damage
BAX↑, Cu-induced ROS increased Bax (pro-apoptotic protein), while Bcl2 (anti-apoptotic protein) was decreased
Bcl-2↓,
MMP↓,
Cyt‑c↑, releasing CytC that activated Caspase3
Casp3↑,
ER Stress↑, Nano-CuO) triggers OS by ROS, thus stimulating endoplasmic reticulum (ER)-stress
CHOP↑, which thereby enhanced the expression of CHOP
Apoptosis↑, and CHOP-induced apoptosis
selectivity↑, In fact, autophagy induced by copper can either protect cells from death or contribute to cell death, depending on autophagic flux, which is associated with the concentration of copper.
eff↑, combining artemisinin (ART) and copper peroxide nanodots to enhance autophagy and ferroptosis that produced highly cancer toxic reaction
Pyro↑, Copper-Based Pyroptosis
Paraptosis↑, Copper-Based Paraptosis
Cupro↑, Copper-Based Cuproptosis
ChemoSen↑, studies suggested that Cu-MOFs might be a robust nanoplatform for enhancing chemotherapy activity of Cu-organic compounds.
eff↑, CuS NPs had the ability to directly target cancer cells and then induce in nucleus by modification of RGD and TAT peptides, thus heating cancer cell to exhaustive apoptosis through 980 nm NIR irradiation

1596- Cu,  CDT,    Unveiling the promising anticancer effect of copper-based compounds: a comprehensive review
- Review, NA, NA
TumCD↑, Copper and its compounds are capable of inducing tumor cell death through various mechanisms of action, including activation of apoptosis signaling pathways by reactive oxygen species (ROS), inhibition of angiogenesis, induction of cuproptosis, and p
Apoptosis↓,
ROS↑,
angioG↑,
Cupro↑,
Paraptosis↑,
eff↑, copper nanoparticles can be used as effective agents in chemodynamic therapy, phototherapy, hyperthermia, and immunotherapy.
eff↓, Elevated copper concentrations may promote tumor growth, angiogenesis, and metastasis by affecting cellular processes
selectivity↑, Copper nanoparticles also can selectively attack cancer cells and spare healthy cells This selectivity is attributed to the EPR effect, which enables nanoparticles to accumulate in tumor tissue by exploiting leaky blood vessels
DNAdam↑, Copper has been found to induce DNA damage and oxidation through the formation of ROS.
eff↑, Tumor cells suffering from oxygen deficiency often have an increased concentration of CTR-1, which facilitates the transport of copper(I) into the cells
eff↑, The results demonstrate the promising capabilities of 64CuCl2 as a valuable tool for both diagnosis and therapy in various types of cancer
eff↑, nanoparticles have remarkable properties, including a large surface area to volume ratio, excellent compatibility with living organisms, and the ability to generate ROS when exposed to an acidic tumor microenvironment
eff↑, Several studies have shown that copper nanoparticles can be used as effective agents in chemodynamic therapy (CDT)
Fenton↑, CDT is a promising treatment strategy for cancer that utilizes the in situ Fenton reaction, which is activated by endogenous substances, such as GSH and H2O2 without the need for external energy input
H2O2↑, Copper-based substrates have been developed that generate H2O2 internally and function effectively in weakly acidic tumor microenvironments (TME)
eff↑, metal peroxide nanomaterials and offers a promising strategy to improve CDT efficacy
eff↑, Copper nanoparticles can also be used in phototherapy
eff↑, Copper nanoparticles have also shown success in destroying cancer tissue by hyperthermia. This method is a local anticancer treatment in which cells are exposed to high temperatures.
RadioS↑, promising results when used in combination with radiotherapy or chemotherapy for various tumor types.
ChemoSen↑,
eff↑, copper nanoparticles are promising in cancer immunotherapy because they enhance immune-based therapies
*toxicity↝, Copper is a necessary trace mineral for the human body, but high concentrations of copper can be toxic
other↑, Extensive research has shown that cancer cells require an increased copper content to support their rapid growth compared to normal cells
eff↑, Copper nanoparticles can be used to generate heat when exposed to certain wavelengths of light or alternating magnetic fields.

4830- CUR,    Curcumin and Its Derivatives Induce Apoptosis in Human Cancer Cells by Mobilizing and Redox Cycling Genomic Copper Ions
- in-vitro, Var, NA
eff↑, intracellular copper reacts with curcuminoids in cancer cells to cause DNA damage via ROS generation.
ROS↑, Apoptosis of Cancer Cells Induced by Curcumin Is Mediated by ROS
DNAdam↑,
TumCG↓, Curcumin Inhibits Growth and Induces Apoptosis in Different Types of Cancer Cells
Apoptosis↑,
eff↓, Curcumin-Induced Antiproliferation and Apoptosis in Cancer Cells Are Inhibited by a Cuprous Chelator but Not by Iron and Zinc Chelators
Fenton↑, Generation of superoxide anions may spontaneously result in the synthesis of H2O2, which in turn results in the formation of hydroxyl radicals via oxidation of reduced copper (Fenton reaction)
eff↑, Copper Supplementation Increases the Sensitivity of Normal Breast Epithelial Cells to the Antiproliferative Effects of Curcumin

2821- CUR,    Antioxidant curcumin induces oxidative stress to kill tumor cells (Review)
- Review, Var, NA
*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↑,

1846- dietFMD,  VitC,    A fasting-mimicking diet and vitamin C: turning anti-aging strategies against cancer
- Study, Var, NA
TumCG↓, FMDs delay tumor progression
ChemoSen↑, potentiate chemotherapy efficacy
ChemoSideEff↓, while protecting healthy tissues from chemo-associated side effects in different cancer models
ROS↑, presence of metals, and particularly iron, high dose of vitamin C exerts a pro-oxidant action by generating hydrogen peroxide and hydroxyl radicals via Fenton chemistry
Fenton↑,
H2O2↑,
eff↑, we show that FMD cycles potentiate high-dose vitamin C anti-cancer effects in a range of cancer types
HO-1↓, KRAS-mutant cancer cells respond to vitamin C treatment by up-regulating HO-1, and consequently limiting vitamin C pro-oxidant action. FMD is able to revert HO-1 up-regulation
DNAdam↑, increase in free reactive iron and oxygen species causing DNA damage and cell death
eff↑, we found that the nontoxic FMD + vitamin C combination therapy is as effective as oxaliplatin + vitamin C in delaying tumor progression while the triple FMD, vitamin C and chemotherapy combination treatment is the most effective.

643- EGCG,    New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate
- Analysis, NA, NA
H2O2↑,
Fenton↑,
PDGFR-BB↑,
EGFR↓, EGCG inhibits activities of EGFR, VEGFR, and IGFR
VEGFR2↓,
IGFR↓,
Ca+2↑, EGCG elevates cytosolic Ca2+ levels
NO↑, EGCG-stimulated elevation of cytosolic calcium contributes to NO production by binding to calmodulin
Sp1/3/4↓,
NF-kB↓,
AP-1↓,
STAT1↓,
STAT3↓,
FOXO↓, FOXO1
mtDam↑,
TumAuto↑,

642- EGCG,    Prooxidant Effects of Epigallocatechin-3-Gallate in Health Benefits and Potential Adverse Effect
ROS↑, under high-dose conditions. Autooxidation of EGCG generates substantial ROS
H2O2↑, One EGCG molecule could produce more than two H2O2 molecules
Apoptosis↑,
Trx↓, High concentration of EGCG inactivated Trx/TrxR via the formation of EGCG-Trx1 and EGCG-TrxR conjugates
TrxR↓, High concentration of EGCG inactivated Trx/TrxR via the formation of EGCG-Trx1 and EGCG-TrxR conjugates
JNK↑,
HO-1↑,
Fenton↑,

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

4567- MFrot,    Oncogenic pathways and the electron transport chain: a dangeROS liaison
- Review, Var, NA
ROS↑, In this review, we focus on the ETC as a source of ROS and its modulation by oncogenic pathways, which generates a vicious cycle that resets ROS levels to a higher homoeostatic set point, sustaining the cancer cell phenotype.
ETC↓, Electrons leaking from the ETC can prematurely react with oxygen, resulting in the generation of reactive oxygen species (ROS).
other↝, ETC-derived ROS are pivotal regulators of cell fate, given the central role of mitochondria in life and death.
Fenton↑, The hydroxyl radical (•OH) is a highly damaging ROS with an extremely short half-life that is generated from H2O2 in the presence of iron or copper through the Fenton reaction.
RNS↑, O2•– can also interact with nitric oxide (NO), generating the reactive nitrogen species (RNS) peroxynitrite (ONOO−), which controls signalling molecules through the nitration of tyrosine residues

1744- RosA,    Therapeutic Applications of Rosmarinic Acid in Cancer-Chemotherapy-Associated Resistance and Toxicity
- Review, Var, NA
chemoR↓, Recently, several studies have shown that RA is able to reverse cancer resistance to first-line chemotherapeutics
ChemoSideEff↓, as well as play a protective role against toxicity induced by chemotherapy and radiotherapy
RadioS↑, RA decreased radiation-induced ROS with RA by 21% compared to control
ROS↓, mainly due to its scavenger capacity
ChemoSen↑, recent years, evidence has emerged demonstrating the ability of RA to act as a chemosensitizer
BioAv↑, bioavailability of RA have been studied in animal models, revealing rapid absorption in the stomach and intestine
Half-Life↝, Urine was the primary route of RA excretion, with 83% of the total metabolites excreted during the period from 8 to 18 h after RA administration
antiOx↑, RA, well known for its antioxidant properties,
ROS↑, has recently been identified as a potential pro-oxidant in the presence of superoxide anions.
Fenton↑, Studies indicate that RA can facilitate the reduction of Cu (II) to Cu (I) and Fe (III) to Fe (II) leading to Fenton-type reactions that generate reactive hydroxyl radicals (HO˙)
DNAdam↑, These radicals are implicated in DNA damage and induction of apoptosis in cancer cells
Apoptosis↑,
CSCs↓, RA has demonstrated potential in controlling breast cancer stem cells (CSCs)
HH↓, RA inhibits stem-like breast cancer cells by targeting the hedgehog signaling pathway and modulating the Bcl-2/Bax ratio at concentrations of 270 and 810 μM
Bax:Bcl2↑,
MDR1↓, It has been observed to downregulate P-glycoprotein (P-gp) expression and decrease MDR1 gene transcription, thereby reversing MDR.
P-gp↓,
eff↑, RA has been reported to modulate the ADAM17/EGFR/AKT/GSK3β signaling axis in A375 melanoma cells, potentially enhancing synergy with cisplatin
eff↑, RA has demonstrated effectiveness in enhancing chemosensitivity to 5-FU, a commonly used chemotherapy agent for gastrointestinal cancers.
FOXO4↑, By upregulating FOXO4 expression, RA restored the sensitivity of cells to 5-FU
*eff↑, RA has been shown to reduce DOX-induced apoptosis in H9c2 cardiac muscle cells, and reduce intracellular ROS generation through downregulation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), as well as to restore the
*ROS↓,
*JNK↓,
*ERK↓,
*GSH↑, RA has also shown an antioxidant role, which is evidenced by the ability and recovery of levels of glutathione (GSH), hydrogen peroxide (H2O2), and superoxide radicals (O2·), reducing the expression of malondialdehyde
*H2O2↑,
*MDA↓,
*SOD↑, regulating the expression of antioxidant enzymes such as superoxide dismutase (SOD), as well as upregulating catalase heme oxygenase-1, resulting in significantly improved viability
*HO-1↑,
*CardioT↓, The cardioprotective effect of RA
selectivity↑, RA blocked caspases 3 and 9 activation, cytochrome c release, and ROS generation induced by cisplatin in HEI-OC1(normal)cells

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

3292- SIL,  Fe,    Anti-tumor activity of silymarin nanoliposomes in combination with iron: In vitro and in vivo study
- in-vitro, BC, 4T1 - in-vivo, BC, 4T1
*antiOx↑, Silymarin (SLM) has been extensively investigated due to its potent antioxidant properties and demonstrated efficacy against cancer cells.
ROS↑, we hypothesized that the simultaneous administration of iron (Fe) could alter the antioxidant characteristic of SLM nanoliposomes (SLM Lip) to a prooxidant state
OS↑,
Weight↑,
TumVol↓,
eff↑, In the current study, silymarin nanoliposomes showed higher toxicity on 4 T1 cells when combined with iron sucrose.
Fenton↑, By exchanging iron species during the Fenton reaction (Fe3+ ↔ Fe2+), the ROS levels could increase

2202- SK,    Enhancing Tumor Therapy of Fe(III)-Shikonin Supramolecular Nanomedicine via Triple Ferroptosis Amplification
- in-vitro, Var, NA
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

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.

4468- VitC,  SSE,    Selenium modulates cancer cell response to pharmacologic ascorbate
- in-vivo, GBM, U87MG - in-vitro, CRC, HCT116
eff↓, In vivo, dietary selenium deficiency resulted in significant enhancement of ascorbate activity against glioblastoma xenografts
TumCD↑, pharmacologic ascorbate raises the serum ascorbate concentration into the millimolar range, a concentration at which ascorbate has been shown to kill cancer cells in vitro
ChemoSen↑, Pharmacologic ascorbate has been shown to synergize with multiple chemotherapeutic agents in animal models and is well-tolerated in human patients [1,4], motivating ongoing clinical trials.
ROS⇅, Indeed, the role of ascorbate as either a pro- or anti-oxidant has been suggested to depend on concentration, with low doses mitigating ROS and high doses generating them
DNAdam↑, H2O2 generation by ascorbate has been associated with DNA damage and subsequent PARP activation, which can deplete NAD and thereby inhibit glycolysis
PARP↑,
NAD↓,
Glycolysis↓,
Fenton↑, Ascorbate cytotoxicity depends on the intracellular labile iron pool (Fig 1a) [3,9]. One explanation for this phenomenon is that ascorbate-generated H2O2 causes toxicity through Fenton chemistry
lipid-P↑, extensive lipid peroxidation
eff↓, More generally, they establish dietary selenium depletion as a potential means of sensitizing tumors to free radical stress.
H2O2↑, High concentrations (mM) of ascorbate have been shown to generate H2O2 in vitro
other↝, Selenium supplementation has been shown to protect cells against iron-dependent cell death by supporting increased expression of selenoproteins, including GPX4, which defend against oxidative stress

606- VitC,    Understanding the Therapeutic Potential of Ascorbic Acid in the Battle to Overcome Cancer
- Review, NA, NA
ROS↑, millimolar (mM) concentrations, also functions as a pro-oxidant
H2O2↑,
Fenton↑, elevated copper concentrations ... made cancer cells vulnerable to the ROS-generated selective cytotoxicity of copper and ascorbic acid

599- VitC,    Generation of Hydrogen Peroxide in Cancer Cells: Advancing Therapeutic Approaches for Cancer Treatment
- Review, NA, NA
H2O2↑,
DNAdam↑,
ROS↑,
Fenton↑,
Apoptosis↑, Moderate concentrations of H2O2 typically induce apoptosis
necrosis↑, higher H2O2 concentrations induce necrosis

596- VitC,    High-Dose Vitamin C in Advanced-Stage Cancer Patients
- Review, NA, NA
ChemoSideEff↓, reducing cancer-related symptoms, such as fatigue and bone pain
ROS↑, is able to reduce catalytic metals such as Fe3+ to Fe2+ and Cu2+ to Cu+, increasing the pro-oxidant chemistry of these metals and facilitating the generation of reactive oxygen species
H2O2↑, Reactions of ascorbate with oxygen or with free transition metal ions lead to the generation of superoxide, H2O2 and highly reactive oxidants, such as the hydroxyl radical by promoting the Fenton chemistry
Fenton↑,
Hif1a↝, Ascorbate regulates the transcription of hypoxia inducible factor-1α (HIF-1α)
Dose↑, Results obtained from in vitro studies revealed that millimolar ascorbate plasma concentrations, achievable only after intravenous vitamin C administration, are cytotoxic to fast-growing malignant cells.
BioAv↓, For this reason, ascorbate concentration in plasma does not exceed 100 μmol/L when it is supplied orally with food; even with oral supplementation approaching maximum tolerated doses, it is always <250 μmol/L
Dose↝, 100 mg, the concentration of ascorbate in daily fasting plasma reaches a plateau between 50–60 µmol/L [24]. Whereas increasing the daily dose ten times to 1000 mg gives only a slight increase in plasma concentration to 70–85 μmol/L
Half-Life↝, high concentrations are relatively transient due to the rapid clearance by the kidneys resulting in a half-life of about 2 h in circulation
IL1β↓, IVC (15–50 g up to three times a week) resulted in reduced CRP levels (in 76 ± 13% of study participants) and reduced concentration of pro-inflammatory cytokines (IL-1α, IL-1β, IL-2, IL-8, tumor necrosis factor TNF-α)
IL2↓,
IL8↓,
TNF-α↓,

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

3114- VitC,    Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression
- in-vitro, AML, NA
TET2↑, Treatment with vitamin C, a cofactor of Fe2+ and α-KG-dependent dioxygenases, mimics TET2 restoration by enhancing 5-hydroxymethylcytosine formation in Tet2-deficient mouse HSPCs
eff↑, enhances the efficacy of PARP inhibition in suppressing leukemia progression.
ROS↑, High levels of vitamin C can lead to reactive oxygen species (ROS) production via the Fenton reaction
Fenton↑,
Hif1a↓, One study suggested that vitamin C decreases viability of human leukemia cell lines by promoting downregulation of HIF1α and the anti-apoptotic genes, BCL2, BCL2L1, and MCL1


Showing Research Papers: 1 to 33 of 33

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 33

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Fenton↑, 33,   Ferroptosis↑, 5,   GPx4↓, 4,   GSH↓, 7,   H2O2↑, 10,   HNE↑, 1,   HO-1↓, 1,   HO-1↑, 4,   Iron↓, 1,   Iron↑, 6,   i-Iron↓, 1,   lipid-P↓, 1,   lipid-P↑, 4,   NQO1↑, 1,   NRF2↓, 2,   NRF2↑, 1,   RNS↑, 1,   ROS↓, 1,   ROS↑, 29,   ROS⇅, 1,   i-ROS↑, 1,   mt-ROS↑, 1,   Trx↓, 1,   TrxR↓, 1,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 1,   FTH1↓, 1,   NCOA4↝, 1,   Tf↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   ETC↓, 1,   MMP↓, 2,   mtDam↑, 3,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   ATG7↑, 1,   Glycolysis↓, 1,   NAD↓, 2,  

Cell Death ⓘ

Akt↓, 2,   p‑Akt↓, 1,   Apoptosis↓, 1,   Apoptosis↑, 12,   BAX↑, 2,   Bax:Bcl2↑, 1,   Bcl-2↓, 2,   Casp3↑, 3,   Casp9↑, 2,   Cupro↑, 2,   Cyt‑c↑, 4,   Ferroptosis↑, 5,   JNK↑, 3,   p‑JNK↑, 1,   MAPK↑, 2,   necrosis↑, 1,   p38↑, 1,   Paraptosis↑, 2,   Pyro↑, 1,   survivin↓, 1,   TumCD↑, 2,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

other↑, 2,   other↝, 2,   sonoS↑, 2,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

ATF6↑, 1,   CHOP↑, 2,   ER Stress↑, 3,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   TumAuto↑, 3,  

DNA Damage & Repair ⓘ

DNAdam↑, 7,   P53↑, 1,   PARP↑, 2,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   cycD1/CCND1↓, 1,   P21↑, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   EMT↓, 1,   ERK↑, 1,   p‑ERK↑, 1,   FOXO↓, 1,   FOXO4↑, 1,   HDAC8↓, 1,   HH↓, 1,   IGFR↓, 1,   mTOR↓, 1,   mTOR↑, 1,   P70S6K↑, 1,   SCF↓, 1,   STAT1↓, 1,   STAT3↓, 2,   TumCG↓, 4,  

Migration ⓘ

AP-1↓, 1,   AP-1↑, 1,   Ca+2↑, 1,   TumCI↓, 1,   TumCP↓, 1,   TumMeta↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   angioG↑, 1,   EGFR↓, 1,   EPR↑, 2,   Hif1a↓, 2,   Hif1a↝, 1,   NO↑, 3,   PDGFR-BB↑, 1,   VEGF↓, 1,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,   IL2↓, 1,   IL8↓, 1,   NF-kB↓, 1,   TNF-α↓, 1,  

Cellular Microenvironment ⓘ

pH↝, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   chemoR↓, 1,   ChemoSen↑, 9,   Dose↑, 1,   Dose↝, 2,   eff?, 1,   eff↓, 5,   eff↑, 29,   eff↝, 1,   Half-Life↝, 2,   MDR1↓, 1,   RadioS↑, 3,   selectivity↑, 9,   TET2↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   Ferritin↓, 1,  

Functional Outcomes ⓘ

chemoPv↑, 1,   ChemoSideEff↓, 3,   OS↑, 1,   TumVol↓, 1,   Weight↑, 1,  
Total Targets: 138

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   GSH↑, 2,   GSTs↑, 1,   H2O2↑, 1,   HO-1↑, 1,   MDA↓, 1,   NRF2↑, 1,   ROS↓, 3,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

NADPH↑, 1,  

Cell Death ⓘ

JNK↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   eff↑, 1,  

Functional Outcomes ⓘ

CardioT↓, 1,   toxicity?, 1,   toxicity↓, 1,   toxicity↝, 2,   toxicity∅, 2,  
Total Targets: 21

Scientific Paper Hit Count for: Fenton, Fenton Reaction
8 Vitamin C (Ascorbic Acid)
5 chemodynamic therapy
5 Copper and Cu NanoParticles
3 Artemisinin
2 Silver-NanoParticles
2 Curcumin
2 EGCG (Epigallocatechin Gallate)
2 Rosmarinic acid
1 Ascorbyl Palmitate
1 Gold NanoParticles
1 Gemcitabine (Gemzar)
1 Baicalein
1 Chrysin
1 Black phosphorus
1 SonoDynamic Therapy UltraSound
1 diet FMD Fasting Mimicking Diet
1 Magnetic Fields
1 immunotherapy
1 Magnetic Field Rotating
1 Silymarin (Milk Thistle) silibinin
1 Iron
1 Shikonin
1 Aflavin-3,3′-digallate
1 Selenite (Sodium)
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#:804  State#:%  Dir#:2
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