The DOI matches its Crossref record; 152 of the 152 references it cites were found in a registry or an index; none of the 131 sources its claims cite is checked for support yet.
The Two Faces of Reactive Oxygen Species in Cancer
Open accessAbstract
Reactive oxygen species (ROS), now appreciated for their cellular signaling capabilities, have a dual role in cancer. On the one hand, ROS can promote protumorigenic signaling, facilitating cancer cell proliferation, survival, and adaptation to hypoxia. On the other hand, ROS can promote antitumorigenic signaling and trigger oxidative stress–induced cancer cell death. To hyperactivate the cell signaling pathways necessary for cellular transformation and tumorigenesis, cancer cells increase their rate of ROS production compared with normal cells. Concomitantly, in order to maintain ROS homeostasis and evade cell death, cancer cells increase their antioxidant capacity. Compared with normal cells, this altered redox environment of cancer cells may increase their susceptibility to ROS-manipulation therapies. In this review, we discuss the two faces of ROS in cancer, the potential mechanisms underlying ROS signaling, and the opposing cancer therapeutic approaches to targeting ROS.
Overview
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Written from the paper’s full text.
TL;DR
Reactive oxygen species (ROS) have dual roles in cancer: they can promote protumorigenic signaling and also trigger antitumorigenic oxidative stress–induced cancer cell death. Cancer cells increase both ROS production and antioxidant capacity, creating an altered redox environment that may make them vulnerable to ROS-manipulation therapies.
Key findings
- Cancer cells often have increased ROS production and increased ROS scavenging compared with normal cells; this altered redox state maintains ROS homeostasis to support proliferation, survival, and hypoxia adaptation while avoiding cell death.
- ROS promote protumorigenic signaling by oxidizing and inactivating phosphatases such as PTEN and PTP1B, activating PI3K/Akt/mTOR and MAPK/ERK pathways, stabilizing HIF-1α, and supporting NF-κB/NRF2 signaling, angiogenesis, and metastasis; mitochondrial O2− from complexes I, II, and III is among 10 mitochondrial sites of O2− production implicated in redox signaling.
- Excessive ROS activate ASK1/JNK and ASK1/p38 signaling to induce cell cycle arrest, senescence, and cancer cell death; p53 loss or mutation, observed in more than 50% of human cancers, can permit ROS accumulation and protumorigenic signaling.
- Therapeutic strategies include decreasing ROS with antioxidants or mitochondria-targeted antioxidants, and increasing ROS with pro-oxidants or antioxidant inhibitors; a screen of 635,000 small molecules identified three compounds that suppress complex III O2− production and prevent HIF-1α stabilization.
Methods
- Narrative review synthesizing published literature on ROS generation, regulation, signaling, and therapeutic targeting in cancer; no primary experimental data are presented.
- Discusses mechanistic studies, mouse models, cancer cell lines, clinical trial results, and chemical screens, but does not describe a systematic search strategy, sample size, or formal quantitative analysis.
Limitations
- The paper states that dietary antioxidant supplementation has shown mixed results, with some large prospective clinical studies reporting increased cancer incidence, and that NRF2 inhibitor development is challenged by specificity.
- The paper notes that normal cells, particularly stem cells, are sensitive to ROS levels, so therapies must selectively target antioxidant pathways used by cancer cells.
- Evident from the text: as a narrative review, it lacks systematic search criteria, risk-of-bias assessment, and quantitative synthesis; many therapeutic claims rest on preclinical models and cited studies rather than new primary data.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
0 of 131 cited sources checked · 0 supported · 0 flagged
None of the sources cited for this claim have been checked yet.
In the paper
“H2O2 is the best described signaling molecule”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS GENERATION AND REGULATION > Types of ROS
What the sources say
- Not checked yetcites Finkel 2011
- Not checked yetcites Reczek & Chandel 2015
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Signaling-associated ROS are produced from two main sources, the mitochondria and membrane-bound NADPH oxidases (NOXs)”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS GENERATION AND REGULATION > Sources of ROS
What the sources say
- Not checked yetcites Brewer et al. 2015
- Not checked yetcites Goncalves et al. 2015
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“NRF2 has been shown to be essential for cancer cell proliferation and tumorigenesis”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS GENERATION AND REGULATION > Regulation of ROS
What the sources say
- Not checked yetcites DeNicola et al. 2011
- Not checked yetcites Jaramillo & Zhang 2013
- Not checked yetcites Satoh et al. 2013
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“tumor suppressor loss can diminish ROS elimination”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS GENERATION AND REGULATION > Regulation of ROS
What the sources say
- Not checked yetcites Schieber & Chandel 2014
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Compared with normal cells, this altered redox environment of cancer cells may increase their susceptibility to ROS-manipulation therapies.”
§ The Two Faces of Reactive Oxygen Species in Cancer > Abstract
What the sources say
- Not checked yetcites Gorrini et al. 2013b
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“NRF2 constitutive upregulation has been observed in many cancer types, including skin, breast, prostate, and lung”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS GENERATION AND REGULATION > Regulation of ROS
What the sources say
- Not checked yetcites No et al. 2014
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“The tumor suppressor p53 has been shown to suppress ROS accumulation by regulating the expression of a variety of antioxidant genes, including SOD2, GPX1, and CAT”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS GENERATION AND REGULATION > Regulation of ROS
What the sources say
- Not checked yetcites Kruiswijk et al. 2015
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Therefore, the fate of ROS as a signaling molecule or toxic agent depends on the type of ROS, its local concentration, and the abundance of antioxidants”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS GENERATION AND REGULATION > Sources of ROS
What the sources say
- Not checked yetcites Chandel & Tuveson 2014
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“tumor suppressors may serve an antioxidant function in normal cells”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS GENERATION AND REGULATION > Regulation of ROS
What the sources say
- Not checked yetcites Gorrini et al. 2013a
- Not checked yetcites Tao et al. 2010
- Not checked yetcites Kruiswijk et al. 2015
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“the loss of NRF2 reduces tumor burden by promoting oxidative stress–induced cancer cell death”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS GENERATION AND REGULATION > Regulation of ROS
What the sources say
- Not checked yetcites DeNicola et al. 2011
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 26
- Probably not a substantial claim. 3
In the paper
“ROS homeostasis is required for normal cell survival and proper cell signaling.”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS GENERATION AND REGULATION > Regulation of ROS
What the sources say
- Not checked yetcites Sena & Chandel 2012
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Although oncogene activation, enhanced metabolism, and hypoxia can increase ROS production”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS GENERATION AND REGULATION > Regulation of ROS
What the sources say
- Not checked yetcites Schieber & Chandel 2014
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Excessive levels of ROS can increase oxidative stress and induce cancer cell death”
§ The Two Faces of Reactive Oxygen Species in Cancer > INTRODUCTION
What the sources say
- Not checked yetcites Nogueira et al. 2008
- Not checked yetcites Trachootham et al. 2006
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“ROS accumulation can occur because ROS production is increased or ROS elimination is decreased”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS GENERATION AND REGULATION > Regulation of ROS
What the sources say
- Not checked yetcites Trachootham et al. 2009
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On the one hand, ROS can promote protumorigenic signaling, facilitating cancer cell proliferation, survival, and adaptation to hypoxia. On the other hand, ROS can promote antitumorigenic signaling and trigger oxidative stress–induced cancer cell death.”
§ The Two Faces of Reactive Oxygen Species in Cancer > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“when p53 is lost or mutated, as observed in more than 50% of human cancers, ROS accumulation can occur, allowing for protumorigenic signaling and cellular transformation”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS GENERATION AND REGULATION > Regulation of ROS
What the sources say
- Not checked yetcites Levine & Oren 2009
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“ROS also oxidize and inactivate MAPK phosphatases, inducing growth factor receptor activation and MAPK/ERK pro-proliferative signaling”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS PROMOTE PROTUMORIGENIC SIGNALING
What the sources say
- Not checked yetcites Seth & Rudolph 2006
- Not checked yetcites Son et al. 2011
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This mechanism, termed redox relay, is a two-step process in which the scavenging enzyme (e.g., PRX or GPX) receives H2O2 oxidation and transfers the oxidation to the target protein.”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS AS SIGNALING MOLECULES > H2O2-Dependent Signal Transduction
What the sources say
- Not checked yetcites Winterbourn 2013
- Not checked yetcites Sobotta et al. 2015
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“the complete disruption of the mitochondrial respiratory chain, which reduces ROS, has been shown to diminish tumorigenesis”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS PROMOTE PROTUMORIGENIC SIGNALING
What the sources say
- Not checked yetcites Weinberg et al. 2010
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“oncogenic Kras-derived mROS activated NF-κB through PKD1 to upregulate pro-proliferative EGFR signaling, leading to the formation of pancreatic precancerous lesions”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS PROMOTE PROTUMORIGENIC SIGNALING
What the sources say
- Not checked yetcites Liou et al. 2016
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ROS promote tumor angiogenesis and metastasis, interrelated processes often associated with a poor prognosis.”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS PROMOTE PROTUMORIGENIC SIGNALING
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“When ROS levels are too high, cell cycle arrest, senescence, and cancer cell death can occur”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS PROMOTE ANTITUMORIGENIC SIGNALING
What the sources say
- Not checked yetcites Ichijo et al. 1997
- Not checked yetcites Moon et al. 2010
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Inactivating mutations in p38 and JNK pathway components have been observed in numerous human tumors, suggesting that these signaling pathways promote cancer cell death”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS PROMOTE ANTITUMORIGENIC SIGNALING
What the sources say
- Not checked yetcites Han & Sun 2007
- Not checked yetcites Kennedy & Davis 2003
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Although the increase in ROS allows for localized signaling to promote cancer cell proliferation and survival, the increase in ROS scavenging reduces distant ROS-mediated oxidative damage and maintains ROS homeostasis”
§ The Two Faces of Reactive Oxygen Species in Cancer > TARGETING ROS FOR CANCER THERAPY
What the sources say
- Not checked yetcites Chandel & Tuveson 2014
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“As tumor cells detach from the extracellular matrix and invade the basement membrane, ROS levels increase and the reduced pool of GSH decreases”
§ The Two Faces of Reactive Oxygen Species in Cancer > ROS PROMOTE ANTITUMORIGENIC SIGNALING
What the sources say
- Not checked yetcites Schafer et al. 2009
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“the small molecule piperlongumine, identified from an unbiased screen, enhanced ROS levels and the selective cell death of cancer cells by diminishing the abundance of reduced GSH”
§ The Two Faces of Reactive Oxygen Species in Cancer > TARGETING ROS FOR CANCER THERAPY > Increasing ROS Levels to Promote Oxidative Stress–Induced Cancer Cell Death
What the sources say
- Not checked yetcites Raj et al. 2011
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The mitochondria-targeted O2− scavenger MitoTEMPO has been shown to block tumor cell migration and inhibit spontaneous tumor metastasis in human and murine models”
§ The Two Faces of Reactive Oxygen Species in Cancer > TARGETING ROS FOR CANCER THERAPY > Decreasing ROS Levels to Prevent Cancer Cell Proliferation
What the sources say
- Not checked yetcites Porporato et al. 2014
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“the mitochondria-targeted antioxidant MitoQ reduced the formation of Kras-driven pancreatic precancerous lesions, suggesting that mROS propagates the protumorigenic signal”
§ The Two Faces of Reactive Oxygen Species in Cancer > TARGETING ROS FOR CANCER THERAPY > Decreasing ROS Levels to Prevent Cancer Cell Proliferation
What the sources say
- Not checked yetcites Liou et al. 2016
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because cancer cells have elevated ROS levels compared with normal cells, they are potentially more vulnerable to oxidative stress–induced cell death by ROS-producing strategies.”
§ The Two Faces of Reactive Oxygen Species in Cancer > TARGETING ROS FOR CANCER THERAPY > Increasing ROS Levels to Promote Oxidative Stress–Induced Cancer Cell Death
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“buthionine sulfoximine (BSO), an inhibitor of glutamate cysteine ligase (GCL), the enzyme required for GSH synthesis, depletes GSH and exhibits anticancer activity”
§ The Two Faces of Reactive Oxygen Species in Cancer > TARGETING ROS FOR CANCER THERAPY > Increasing ROS Levels to Promote Oxidative Stress–Induced Cancer Cell Death
What the sources say
- Not checked yetcites Andringa et al. 2006
- Not checked yetcites Bailey et al. 1997
- Not checked yetcites Griffith & Meister 1979 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“For example, CD44v-expressing human gastrointestinal CSCs have been shown to stabilize the cysteine-glutamate exchange transporter and increase the synthesis of GSH (Ishimoto et al. 2011).”
§ The Two Faces of Reactive Oxygen Species in Cancer > TARGETING ROS FOR CANCER THERAPY > Increasing ROS Levels to Promote Oxidative Stress–Induced Cancer Cell Death
What the sources say
- Not checked yetcites Ishimoto et al. 2011
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“a recent high-throughput screen of 635,000 small molecules against mitochondrial H2O2 production revealed three compounds that specifically suppress complex III O2− production and prevent HIF-1α protein stabilization without impairing the bioenergetic function of the mitochondria”
§ The Two Faces of Reactive Oxygen Species in Cancer > TARGETING ROS FOR CANCER THERAPY > Decreasing ROS Levels to Prevent Cancer Cell Proliferation
What the sources say
- Not checked yetcites Orr et al. 2015
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“It is possible that dietary antioxidants do not efficiently scavenge the pool of protumorigenic signaling ROS and instead promote tumor progression by decreasing the toxicity of ROS distant from their site of production”
§ The Two Faces of Reactive Oxygen Species in Cancer > TARGETING ROS FOR CANCER THERAPY > Decreasing ROS Levels to Prevent Cancer Cell Proliferation
What the sources say
- Not checked yetcites Chandel & Tuveson 2014
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“a high dose of the antioxidant vitamin C has been shown to function as a pro-oxidant (ROS generator), genotype-selective anticancer agent, inducing the cell death of Kras- and Braf-mutant colon cancer cells”
§ The Two Faces of Reactive Oxygen Species in Cancer > TARGETING ROS FOR CANCER THERAPY > Increasing ROS Levels to Promote Oxidative Stress–Induced Cancer Cell Death
What the sources say
- Not checked yetcites Yun et al. 2015
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Moreover, targeting the antioxidant CAT in combination with ROS-generating CDK4 and CDK6 inhibitors has been shown to elevate ROS levels above the threshold and reduce pancreatic ductal adenocarcinoma cell growth (Franco et al. 2016).”
§ The Two Faces of Reactive Oxygen Species in Cancer > TARGETING ROS FOR CANCER THERAPY > Increasing ROS Levels to Promote Oxidative Stress–Induced Cancer Cell Death
What the sources say
- Not checked yetcites Franco et al. 2016
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“LCS-1 impaired the integrity of the mitochondria in breast cancer cell lines, but not in nontumorigenic cell lines, suggesting SOD1 inhibition as a potential therapeutic approach for breast cancer (Papa et al. 2014).”
§ The Two Faces of Reactive Oxygen Species in Cancer > TARGETING ROS FOR CANCER THERAPY > Increasing ROS Levels to Promote Oxidative Stress–Induced Cancer Cell Death
What the sources say
- Not checked yetcites Papa et al. 2014
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“During serine starvation, HCT116 p53-null cancer cells displayed impaired proliferation, decreased levels of GSH, and increased intracellular ROS levels compared with their serine-starved wild-type counterparts (Maddocks et al. 2013).”
§ The Two Faces of Reactive Oxygen Species in Cancer > TARGETING ROS FOR CANCER THERAPY > Increasing ROS Levels to Promote Oxidative Stress–Induced Cancer Cell Death
What the sources say
- Not checked yetcites Maddocks et al. 2013
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A better understanding of the molecular mechanisms of ROS signaling in cancer and the identification of specific ROS targets may provide novel therapeutic avenues for treating cancer.”
§ The Two Faces of Reactive Oxygen Species in Cancer > CONCLUSIONS
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
In the paper
“Additionally, it may be beneficial to combine ROS-producing agents with ROS-scavenging inhibitors to reduce cancer cell adaptation and resistance to chemotherapeutics (Weinberg & Chandel 2015).”
§ The Two Faces of Reactive Oxygen Species in Cancer > TARGETING ROS FOR CANCER THERAPY > Increasing ROS Levels to Promote Oxidative Stress–Induced Cancer Cell Death
What the sources say
- Not checked yetcites Weinberg & Chandel 2015
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
The paper relies on this without support.
Protumorigenic signaling occurs near the site of ROS production.
“Because protumorigenic signaling occurs near the site of ROS production, the use of antioxidants or inhibitors that target the source of ROS generation may prevent tumorigenesis.”
The paper relies on this without support.
Cancer cells have higher levels of ROS production compared with normal cells.
“Furthermore, although initially counterintuitive, pro-oxidant cancer therapy—whereby ROS production is increased or ROS scavenging is decreased, or both—is an attractive approach, given the higher levels of ROS production in cancer cells compared with normal cells.”
The paper relies on this without support.
ROS has a causal role in promoting tumorigenesis.
“Given the causal role of ROS in promoting tumorigenesis and the widely held belief that antioxidants are tumor suppressors, ROS-manipulation strategies have previously focused on antioxidant therapy.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“ROS can either (i) promote protumorigenic signaling supporting the proliferation and survival of cancer cells or (ii) conversely promote antitumorigenic signaling and oxidative stress-induced cancer cell death (Reczek and Chandel 2017).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Reczek and Chandel 2017
Citations
Cites
2 retracted
Selective killing of cancer cells by a small molecule targeting the stress response to ROS
Raj, L., Ide, T., Gurkar, A. U., Foley, M. A., Schenone, M., Li, X., Tolliday, N. J., Golub, T. R., Carr, S. A., Shamji, A. F., et al. (2011) · Nature · doi:10.1038/nature10167 · Cited by 1,040 · cited 17×
“Additionally, it is conceivable that the thiol-containing compounds GSH or reduced TRX recycle the oxidized scavenger back to its reduced state and transmit the signal to the target protein (Shao et al. 2014).”
BackgroundInfluentialRetractedAdhikary, A., Mohanty, S., Lahiry, L., Hossain, D. M. S., Chakraborty, S., & Das, T. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.10.081 · Cited by 79 · cited 1×
“Thus, perturbing these ROS-mitigating pathways may be a viable therapeutic approach for suppressing cancer cell proliferation and metastasis (Adhikary et al. 2010, Wu et al. 2010).”
BackgroundRetractedHow mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207 · cited 2×
“O2− is released into the mitochondrial matrix by complexes I, II, and III, where SOD2 rapidly converts it to H2O2 (Murphy 2009).”
BackgroundThe NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989 · cited 1×
“Although primarily localized to the plasma membrane, NOXs can be found on other membranes, including those of the nucleus, mitochondria, and endoplasmic reticulum (Bedard & Krause 2007).”
BackgroundROS function in redox signaling and oxidative stress
Schieber, M., & Chandel, N. S. (2014) · Current Biology · doi:10.1016/j.cub.2014.03.034 · Cited by 6,931 · cited 2×
“Although oncogene activation, enhanced metabolism, and hypoxia can increase ROS production, tumor suppressor loss can diminish ROS elimination (Schieber & Chandel 2014).”
BackgroundSelf-citationTargeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717 · cited 1×
“However, during hypoxia, the HIF-α protein is allowed to dimerize with the HIF-β subunit and translocate to the nucleus to induce expression of proangiogenic genes, such as vascular endothelial growth factor and genes involved in cell survival, glycolysis, and metastasis (Semenza 2003, 2012).”
BackgroundOxidants, antioxidants, and the degenerative diseases of aging.
Ames, B. N., Shigenaga, M. K., & Hagen, T. M. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.7915 · Cited by 5,958 · cited 1×
“Because high levels of ROS can cause damage to lipids, proteins, and DNA, it was thought that ROS were oncogenic, promoting genomic instability and tumorigenesis (Ames et al. 1993).”
BackgroundThe phosphoinositide 3-kinase pathway
Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621 · cited 1×
“Thus, the ROS-induced PI3K/Akt survival pathway has been shown to be activated in a majority of cancers (Cantley 2002).”
BackgroundTargeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?
Trachootham, D., Alexandre, J., & Huang, P. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2803 · Cited by 5,452 · cited 1×
“ROS accumulation can occur because ROS production is increased or ROS elimination is decreased (Trachootham et al. 2009).”
BackgroundKim, J.-W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.002 · Cited by 3,905 · cited 1×
“This results in an increase in NADPH generation and maintenance of the cellular antioxidant capacity to counterbalance the hypoxia-induced increase in mitochondrial ROS (mROS) (Kim et al. 2006, Ye et al. 2014).”
Background
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Metabolic reprogramming and cancer progression
Faubert, B., Solmonson, A., & DeBerardinis, R. J. (2020) · Science · doi:10.1126/science.aaw5473 · Cited by 2,740
“The exact role of ROS may depend on the stage and type of cancer (85).”
BackgroundReactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638
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Han, S., Liu, Y., Cai, S. J., Qian, M., Ding, J., Larion, M., Gilbert, M. R., & Yang, C. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-0814-x · Cited by 701
Metabolic heterogeneity confers differences in melanoma metastatic potential
Tasdogan, A., Faubert, B., Ramesh, V., Ubellacker, J. M., Shen, B., Solmonson, A., Murphy, M. M., Gu, Z., Gu, W., Martin, M., et al. (2020) · Nature · doi:10.1038/s41586-019-1847-2 · Cited by 509
Metadata
- Authors
- Reczek, C. R., & Chandel, N. S.
- Affiliations
- Northwestern University (US)
- Venue
- Annual Review of Cancer Biology
- Publisher
- Annual Reviews
- Published
- 2017-03-06
- Volume
- 1
- Issue
- 1
- Pages
- 79-98
- ISSN
- 2472-3428 (ISSN-L)
- PMC
- PMC11875389
- OpenAlex
- W2509946779
- Semantic Scholar
- fa6f060895b44afc150511174ef31fd04137e66e
- Cited by
- 602
- References
- 151
- Citations by year
- 2026: 72 · 2025: 50 · 2024: 55 · 2023: 78 · 2022: 134 · 2021: 97 · 2020: 53 · 2019: 37 · 2018: 21 · 2017: 5
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Cancer Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (T32HL076139)
- National Cancer Institute (R01CA123067)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- reactive oxygen species, cancer, ROS signaling, oxidative stress, cancer cell death, hypoxia, antioxidant capacity, redox homeostasis, cell proliferation, cell survival
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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