HIF-Dependent Antitumorigenic Effect of Antioxidants In Vivo

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)230-238
Number of pages9
JournalCancer cell
Volume12
Issue number3
DOIs
StatePublished - Sep 11 2007

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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