The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
HIF-Dependent Antitumorigenic Effect of Antioxidants In Vivo
Open accessAbstract
The antitumorigenic activity of antioxidants has been presumed to arise from their ability to squelch DNA damage and genomic instability mediated by reactive oxygen species (ROS). Here, we report that antioxidants inhibited three tumorigenic models in vivo. Inhibition of a MYC-dependent human B lymphoma model was unassociated with genomic instability but was linked to diminished hypoxia-inducible factor (HIF)-1 levels in a prolyl hydroxylase 2 and von Hippel-Lindau protein-dependent manner. Ectopic expression of an oxygen-independent, stabilized HIF-1 mutant rescued lymphoma xenografts from inhibition by two antioxidants: N-acetylcysteine and vitamin C. These findings challenge the paradigm that antioxidants diminish tumorigenesis primarily through decreasing DNA damage and mutations and provide significant support for a key antitumorigenic effect of diminishing HIF levels.
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In the citing paper
“Interestingly, our NAC treated scramble shRNA expressing cells did form tumors, which is not consistent with the aforementioned study.”
From SirT3 suppresses hypoxia inducible factor 1α and tumor growth by inhibiting mitochondrial ROS production (2011) · cites this paper as Gao et al., 2007
In the citing paper
“Previously it was reported that NAC administration completely inhibits tumor formation in xenograft models (Gao et al., 2007).”
From SirT3 suppresses hypoxia inducible factor 1α and tumor growth by inhibiting mitochondrial ROS production (2011) · cites this paper as Gao et al., 2007
In the citing paper
“ROS signals are sufficient to trigger the stabilization of HIFα (21, 31), and a recent study indicates that antioxidant therapy significantly inhibits tumor progression in vivo by inhibiting HIF activation (18).”
From Loss of the SdhB, but Not the SdhA, Subunit of Complex II Triggers Reactive Oxygen Species-Dependent Hypoxia-Inducible Factor Activation and Tumorigenesis (2008) · cites this paper as [18]
In the citing paper
“there is growing evidence that HIF1α-dependent tumour growth may be inhibited by ascorbate78,79.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [79]
In the citing paper
“In a mouse model of myc-driven tumorigenesis, tumor growth is inhibited by treatment with antioxidants 70.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [70]
In the citing paper
“However, the effect of antioxidant treatment was a result of the inhibition of HIF accumulation: expression of a stable HIF mutant alone could provide resistance to antioxidant treatment.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [70]
Citations
Cites
Targeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717
Self-citationHypoxia signalling in cancer and approaches to enforce tumour regression
Pouysségur, J., Dayan, F., & Mazure, N. M. (2006) · Nature · doi:10.1038/nature04871 · Cited by 1,676
Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing
Guzy, R. D., Hoyos, B., Robin, E., Chen, H., Liu, L., Mansfield, K. D., Simon, M. C., Hammerling, U., & Schumacker, P. T. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.001 · Cited by 1,545
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation
Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., & Simon, M. C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9361-9374.2003 · Cited by 1,386
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The antioxidant function of the p53 tumor suppressor
Sablina, A. A., Budanov, A. V., Ilyinskaya, G. V., Agapova, L. S., Kravchenko, J. E., & Chumakov, P. M. (2005) · Nature Medicine · doi:10.1038/nm1320 · Cited by 1,137
A Biologic Definition of Burkitt's Lymphoma from Transcriptional and Genomic Profiling
Hummel, M., Bentink, S., Berger, H., Klapper, W., Weßendorf, S., Barth, T. F. E., Bernd, H., Cogliatti, S., Dierlamm, J., Feller, A. C., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa055351 · Cited by 1,002
Zhang, H., Gao, P., Fukuda, R., Kumar, G., Krishnamachary, B., Zeller, K. I., Dang, C. V., & Semenza, G. L. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.04.001 · Cited by 885
Self-citationc-Myc Can Induce DNA Damage, Increase Reactive Oxygen Species, and Mitigate p53 Function
Vafa, O., Wade, M., Kern, S., Beeche, M., Pandita, T. K., Hampton, G. M., & Wahl, G. M. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00520-8 · Cited by 876
HIF-2α Promotes Hypoxic Cell Proliferation by Enhancing c-Myc Transcriptional Activity
Gordan, J. D., Bertout, J. A., Hu, C.-J., Diehl, J. A., & Simon, M. C. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.02.006 · Cited by 781
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Role of Indian Ginseng Withaferin A in ROS-Induced Cancer Chemoprevention and Cancer Therapy
Mounica, P. K., Devabattula, G., & Godugu, C. (2022) · Handbook of Oxidative Stress in Cancer: Therapeutic Aspects · doi:10.1007/978-981-16-1247-3_22-1
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The Implication of Anti-angiogenic Treatment of Malignancies on Human Metabolism
Obad, N., & Bjerkvig, R. (2019) · Springer eBooks · doi:10.1007/978-3-319-33673-2_35
Galli, T. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735525717.793562709
Hu, M., Chen, G.-H., & Yang, Y. (2021) · Research Square · doi:10.21203/rs.3.rs-673133/v1
Kuhn, B. T. (2022) · doi:10.21248/gups.68614
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Mounica, P. K., Devabattula, G., & Godugu, C. (2022) · Handbook of Oxidative Stress in Cancer: Therapeutic Aspects · doi:10.1007/978-981-16-5422-0_22
Bertout, J. A., Patel, S. A., Fryer, B. H., Durham, A. C., Covello, K. L., Olive, K. P., Goldschmidt, M. H., & Simon, M. C. (2023) · doi:10.1158/0008-5472.c.6499787.v1
Age-Related Metabolic Reprogramming in Cancer Cell Plasticity
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Vitamin B1 protects against Aβ1-42-induced HIF-1α activation and neurotoxicity
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Synthetic Lethality and Metabolism in Ewing Sarcoma : Knowledge Through Silence
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Giessner, C. (2015) · theses.fr (ABES) · doi:10.70675/ad91f126zab69z4befzb47bz6ebe23e41f19
Role of hypoxia and metabolism in the maturation of hemodialysis arteriovenous fistulas
Sadaghianloo, N. (2018) · theses.fr (ABES) · doi:10.70675/dd46cd88z0b28z473fz9684zb469ec41bcf3
Malard, E. (2023) · theses.fr (ABES) · doi:10.70675/74964e84zb117z490dzb121zf85fa183d480
Wattanathamsan, O., Chantaravisoot, N., Bootsri, R., Kalpongnukul, N., Youngsanbhu, N., Oliva, C. R., Griguer, C. E., & Buranasudja, V. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27114964
STK11 deficiency drives NSCLC immune resistance via ETNK2-mediated phosphoethanolamine accumulation
Zhang, W., Hu, J., & Zhang, Z. (2026) · International Immunology · doi:10.1093/intimm/dxag048
Tumor Microenvironment-Responsive Smart Nanodrug Delivery Systems for Cancer Theranostics
Wen, X., Jiang, Y., Yang, H., & Sun, Q. (2026) · Journal of Nanotheranostics · doi:10.3390/jnt7040023
Geer, M. A. (2015) · DukeSpace (Duke University)
Metadata
- Authors
- Gao, P., Zhang, H., Dinavahi, R., Li, F., Xiang, Y., Raman, V., Bhujwalla, Z. M., Felsher, D. W., Cheng, L., Pevsner, J., Lee, L. A., Semenza, G. L., & Dang, C. V.
- Affiliations
- Johns Hopkins University (US)
- Stanford Medicine (US)
- Corresponding author
- Dang, Chi V.
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2007-09
- Volume
- 12
- Issue
- 3
- Pages
- 230-238
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC2084208
- OpenAlex
- W2143182501
- Cited by
- 523
- References
- 41
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 15 · 2023: 28 · 2022: 25 · 2021: 36 · 2020: 21 · 2019: 23 · 2018: 23 · 2017: 38 · 2016: 32 · 2015: 26 · 2014: 46 · 2013: 22 · 2012: 30
- FWCI
- 11.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA057341, CA91596, CA 51497, P50CA103175, R37CA051497, R01CA091596, R01CA051497)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- 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
- Keywords
- antioxidants, HIF-1, anti-tumorigenic effects, prolyl hydroxylase 2, von Hippel-Lindau protein, N-acetylcysteine, vitamin C, reactive oxygen species, genomic instability, DNA damage, lymphoma xenografts
- MeSH terms
- Acetylcysteine, Animals, Antineoplastic Agents, Antioxidants, Ascorbic Acid, Cell Line, Humans, Mice, Transgenic, Mutation, Genomic Instability, Mice, Hypoxia-Inducible Factor 1
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