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
AI snapshot
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
97 Not checked yet · 12 Own interpretation
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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None 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
boostedstates a cause- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In 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
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In 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
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None 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
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
boostedstates a cause- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It 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
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It 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
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates a cause- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
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Helping Leukemia Cells to Die with Natural or Chemical Compounds Through H2O2 Signaling
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Translational Reprogramming of mRNA in Oxidative Stress and Cancer
Chakraborty, A. (2022) · Handbook of Oxidative Stress in Cancer: Therapeutic Aspects · doi:10.1007/978-981-16-1247-3_245-1
The Role of Reactive Oxygen Species on Cellular Fate and Function of Tumor-Infiltrating Lymphocytes
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Pristimerin in Oxidative Stress and Use in Cancer
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Oxidative Stress: A Double Edged Sword in Cancer
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Translational Reprogramming of mRNA in Oxidative Stress and Cancer
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Role of MicroRNA in ROS Modulation and Its Implication in Lung Cancer and Therapeutics
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Diferenças sexuais nas redes de regulação gênica durante o período fetal do neurodesenvolvimento
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Introduction to Heavy Metals and Their Toxicity
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“(17) Glioma cells have been shown to accumulate large gene mutation loads, not only in the nucleus but also in the mitochondria, again permitting the accumulation of additional oncogenic characteris‐ tics.”
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McDonald, R. C., Fischer, A. H., & Rusckowski, M. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.27.596060
“The rapid response of the OGBN device in tissue results from the normal scavenging of singlet oxygen species formed at the phosphor by non-enzymatic molecules, such as glutathione and antioxidant enzymes present in the intercellular region 24 .”
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Shah, M. R., Jabri, T., & Khalid, M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-22389-1.00006-7
Polloni, L., Costa, T. R., Morais, L. P., Borges, B. C., Teixeira, S. C., Fernandes, T. A. D. M., Correia, L. I. V., Bastos, L. M., Soares, A. M., Silva, M. J. B., et al. (2024) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2024.111361
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“Elevated reactive oxygen species (ROS) production leads to damage to DNA, lipids, and proteins, thereby promoting the proliferation and survival of cancer cells (Reczek and Chandel 2017).”
Iron Modulation Enhances Anticancer Activity of Atorvastatin in SH-SY5Y Neuroblastoma Cells
ALTUNKAYNAK-CAMCA, H. O., ELÇİ, M. P., Çetinkaya, S., Eşi̇m, Ö., Yücel, Ç., Özkan, C. K., Erdem, O., & Özkan, Y. (2025) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.1007/s44411-025-00359-3
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Distribution, phytochemistry and pharmacological properties of the genus Hugonia
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Oxidative Stress and Pathophysiology of Chronic Disease
Balaji, S., Pandian, M. S., Ganesamoorthy, R., Parameswari, R., & Babujanarthanam, R. (2026) · Springer eBooks · doi:10.1007/978-981-96-9670-3_3 · Cited by 1
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Glutathione is critical for NK cell-mediated immunity
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Mitochondria, microbiota, and cancer
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Repurposing Hetrombopag for Multiple Myeloma by Targeting PNPO: A Celastrol‐Inspired Approach
Yu, T., Wang, C., Xie, J., Wei, Y., Cui, H., Zhang, H., Zhou, F., Deng, Z., Yang, Y., & Gu, C. (2026) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.70227
“ROS, encompassing highly reactive molecules like the hydroxyl radical (•OH), hypochlorous acid (HOCl) and organoid hydrop-eroxides (ROOH) [43], are inevitable metabolic byproducts generated primarily during cellular respiration.”
Modulation de l'activation des lymphocytes T et des réponses anti-tumorales par le fer
Porte, S. (2022) · theses.fr (ABES) · doi:10.70675/4251e200zd50ez4a76zb869zb97fa8d3e879
Leong, Y. Q., Koh, R. Y., Yap, C. G., Chye, S. M., & Ng, K. Y. (2026) · BioMed Research International · doi:10.1155/bmri/2222343
Mechanism‐Aware Deep Learning Maps the Redox Landscape of Cancer‐Relevant Antioxidants
Satija, S., Solanki, S., & Ahuja, G. (2026) · Chemistry - Methods · doi:10.1002/cmtd.202500160
Redox rhythms promote fitness by modulating ageing-dependent reprogramming
Wang, X., Cui, S.-S., Li, X.-K., Qu, S., Chang, W., Tang, A., Jin, Y., Peng, S.-J., Wang, H.-P., Fang, X.-Q., et al. (2026) · Nature Metabolism · doi:10.1038/s42255-026-01515-x · Cited by 2
Tanoy, N. M., Chowdhury, M. N., Tasnim, Z., Riya, M. R. R., Momin, M. A., Sadekuzzaman, M., Mow, S. I., Sabuj, M. S. S., Talha, M. M. H., & Akanda, M. R. (2026) · Pathology - Research and Practice · doi:10.1016/j.prp.2026.156495
Vega‐Baudrit, J. R., & Corrales-Ureña, Y. R. (2026) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2026.1814492
“…basal reactive oxygen species (ROS) generated by oncogenic signaling, mitochondrial dysfunction, and metabolic rewiring; moderate ROS can sustain pro-survival pathways, whereas excessive ROS can exceed antioxidant capacity and trigger cell death (Reczek and Chandel, 2017; Trachootham et al., 2009).”
A Narrative Review of In Vivo Studies on the Role of Reactive Oxygen Species in Ovarian Cancer
Lee, J., Yeo, S. G., Kim, H. O., Lee, J. M., Singh, M. K., Kim, S. S., Oh, T. I., & Park, D. C. (2026) · Antioxidants · doi:10.3390/antiox15050540
“This dual nature is highlighted in the context of cancer, where ROS can promote cell proliferation/survival signaling and hypoxic adaptation, but oxidative stress beyond a certain threshold can induce cell death and lead to antitumor outcomes [6].”
Reducing Zinc Oxide Toxicity via Surface Modification: Emerging Strategies for Cosmetic Applications
Dang, T. P., Thy, L. T. M., Nguyen, M. D., et al. (2026) · Comments on Inorganic Chemistry · doi:10.1080/02603594.2026.2668346
Zafar, R., Pham, T. D., Vakafua, L., Reed, T., & Seyedasli, N. (2026) · Pharmaceuticals · doi:10.3390/ph19050769
“ROS can also induce anti-cancer signalling cascades by damaging cell components through oxidation and inhibiting the cell cycle, and this can limit tumour development and induce cancer cell death [156,157].”
Yen, W., Liu, S. M., Jiang, S.-S., et al. (2026) · Cancer Cell International · doi:10.1186/s12935-026-04361-9
“At high levels, ROS can induce cytotoxicity, whereas moderate levels can support tumor cell survival and signaling pathways associated with cancer progression [36, 37].”
Fiorino, S., Hong, W., de Biase, D., Mastrangelo, L., Maccioni, F., Grottesi, A., Ambrosi, F., Pincigher, L., Lari, F., Bergamini, C., et al. (2026) · Cancers · doi:10.3390/cancers18121932
“The change in the composition of malignant pancreatic tissue is associated with the alteration of its oxygenation and nutrient intake [85,118,225].”
InfluentialRibeiro, E., & Vale, N. (2026) · Membranes · doi:10.3390/membranes16070217
“Reactive oxygen species (ROS) play a central and context-dependent role in cancer biology, functioning both as signaling mediators and as drivers of cellular damage [80].”
Recent advances in phytomedicine-based nano-antioxidants for redox-modulated cancer therapy
Faridi, U. A., Almutairi, F. M., Sakran, M., Zidan, N., Alalawy, A. I., Al-Awthan, Y., Akhtar, Q., & Atteia, H. (2026) · Cancer Nanotechnology · doi:10.1186/s12645-026-00401-1
You, Z., Chen, S., Chen, X., et al. (2026) · BMC Cancer · doi:10.1186/s12885-026-16402-7
“Changes in the oxidative stress environment, as previously discussed, may lead to base mismatches during DNA repair, increasing C > T transition frequency [17].”
Double-edged role of antioxidants and oxidative stress: Focusing on cancer therapy and resistance
Rafieian, A., Maroufi, M., Abduridha, M. S., & Kordkatouli, M. (2026) · Journal of Herbmed Pharmacology · doi:10.34172/jhp.53694
“ROS are known to have an intricate role in cancer, which can act both as an initiator and an inhibitor of cancer formation, depending on their concentration and location in cancer cells (41,42).”
Mao, J., & Wang, K. (2026) · Clinical and Translational Medicine · doi:10.1002/ctm2.70699
“96,97 Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are a subset of polymorphonuclear myeloid cells abnormally differentiated from bone marrow under pathological conditions.”
Oxidative Stress and Redox Imbalance in Cellular Damage
Lopez-Garcia, M., Ramírez-Hernández, A., de la Rosa-Cordero, A. A., Vergara-Tamayo, E. A., Bracho-Velasco, M., Aguilar-Reyes, O. S., & O’Neill-Suárez, S. (2026) · IntechOpen eBooks · doi:10.5772/intechopen.1016699
Jin, J. Y., Hwangbo, D. H., Choi, S., Kim, Y. R., Kim, G., & Lee, E. J. (2026) · ACS Applied Polymer Materials · doi:10.1021/acsapm.6c01197
Rzeski, W. (2026) · Cells · doi:10.3390/cells15151352
“Moderate mitochondrial reactive oxygen species (ROS) signaling contributes to developmental transitions and stem cell regulation [4,6], whereas sustained oxidative stress compromises viability and promotes damage accumulation [5,7].”
Lee, J., Yeo, S. G., Kim, H. O., Lee, J. M., Singh, M. K., Kim, S. S., Oh, T. I., & Park, D. C. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1878450
“In cancer, increased ROS production and the reorganization of antioxidant defense systems occur simultaneously, and tumor cells are thought to maintain a growth-and survival-favorable state by regulating this redox balance (5).”
Okonkwo, C. P., Obiadi, M. C., Anyogu, A. A., Ndubuisi, J. O., Asogwa, B. C., & Ayogu, J. I. (2026) · Research Square · doi:10.21203/rs.3.rs-10538856/v1
Beyond Food Preservation: Translational Perspectives of Synthetic Antioxidants
Vergara, D., Lizama, F., Arias-Fuentes, C., et al. (2026) · Antioxidants · doi:10.3390/antiox15080973
“In this context, tumor cells exhibit elevated levels of ROS, which can play a dual role: on the one hand, promoting pro-tumor signaling (favoring cell survival and proliferation) and, on the other, inducing anti-tumor signaling through the generation of oxidative stress [33].”
Austin, J., Djam, K. H., Lee, B. H., et al. (2026) · Methods in molecular biology · doi:10.1007/978-1-0716-5210-7_14
Design, synthesis, and antitumor evaluation of celastrol derivatives targeting PRDX3
Zhao, Y., Cai, H., Zuo, L., Xu, T., Chen, M., Dong, K., Li, X., Chen, H., Liu, Y., Liu, C., et al. (2026) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2026.119220
Catalase Defines Radiotherapy Resistance and a Therapeutic Vulnerability in Rhabdomyosarcoma
Codenotti, S., Marampon, F., Megiorni, F., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27167147
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Pinto, L., Silva, J. P. N., Monteiro, L. S., et al. (2026) · Applied Sciences · doi:10.3390/app16168015
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Bai, Y., & Chen, W. (2026) · Frontiers in Physiology · doi:10.3389/fphys.2026.1931732
“ROS, produced mainly at complexes I and III of the electron transport chain, serve as signaling molecules at physiological levels (Sullivan and Chandel, 2014; Reczek and Chandel, 2017).”
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“Accumulating evidence indicates that disruption of redox homeostasis and cellular energy metabolism is a critical determinant of prostate cancer cell fate and has emerged as a promising therapeutic target [33–36].”
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Decoupling metabolic defense: Mutational and recombinational chaos in Sod1-deficient cells
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“Cancer cells frequently exhibit aberrant redox homeostasis; while moderate ROS levels promote pro-tumorigenic signaling and hyper-proliferation, excessive ROS production is cytotoxic [38].”
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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
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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.
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