Cited by 523Cancer, Hypoxia, and MetabolismRedox biology and oxidative stressCancer and biochemical research

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HIF-Dependent Antitumorigenic Effect of Antioxidants In Vivo

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Gao, Ping, Zhang, Huafeng, Dinavahi, Ramani, Li, Feng, Xiang, Yan, Raman, Venu, Bhujwalla, Zaver M., Felsher, Dean W., Cheng, Linzhao, Pevsner, Jonathan, Lee, Linda A., Semenza, Gregg L., Dang, Chi V.·2007·Cancer Cell

DOI 10.1016/j.ccr.2007.08.004PMC PMC2084208

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Abstract

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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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: Gao, Ping
Zhang, Huafeng
Li, Feng
Raman, Venu
Bhujwalla, Zaver M.
Felsher, Dean W.
Cheng, Linzhao
Pevsner, Jonathan
Semenza, Gregg L.
Dang, Chi V.
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2007-09
Volume: 12
Issue: 3
Pages: 230-238
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2007.08.004
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2182 d)
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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