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      HIF-Dependent Antitumorigenic Effect of Antioxidants In Vivo

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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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          Author and article information

          Journal
          Cancer Cell
          Cancer Cell
          Elsevier BV
          15356108
          September 2007
          September 2007
          : 12
          : 3
          : 230-238
          Article
          10.1016/j.ccr.2007.08.004
          2084208
          17785204
          c7fb898a-877c-4048-921f-ee798489f025
          © 2007

          https://www.elsevier.com/tdm/userlicense/1.0/

          https://www.elsevier.com/open-access/userlicense/1.0/

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