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HIF-dependent antitumorigenic effect of antioxidants in vivo.

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.

SUBMITTER: Gao P

PROVIDER: S-EPMC2084208 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature

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HIF-dependent antitumorigenic effect of antioxidants in vivo.

Gao Ping P Zhang Huafeng H Dinavahi Ramani R Li Feng F Xiang Yan Y Raman Venu V Bhujwalla Zaver M ZM Felsher Dean W DW Cheng Linzhao L Pevsner Jonathan J Lee Linda A LA Semenza Gregg L GL Dang Chi V CV

Cancer cell 20070901 3

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. Ecto ...[more]

PMID: 17785204

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Project description:ObjectiveTo study the effect of Antioxidants supplementation in reducing oxidative stress induced in acute amitriptyline poisoning cases.Design and methodsWe compared the effect of supplementation of treatment of acute amitriptyline poisoning cases with alpha lipoic acid alone or with vitamin C, with that of those receiving only routine standard treatment (RST) as a control group.A total of 132 subjects divided into 5 groups were selected from IMCU (Intensive Medical Care Unit) and Toxicology Ward, Govt. General Hospital, Chennai, India. The study was restricted to grade 1 coma in poisoned subjects per the Edinburg scale. Each of the subjects was in the groups were supplemented with either placebo, RST, RST with vitamin C, RST with ALA, or RST with vitamin C and ALA.Acute anti-depressant poisoning (especially with amitriptyline) induced oxidative stress caused lipid peroxidation. Plasma cholinesterases (chE) play a major role in combating this effect. A determination of the level of cholinesterase (chE) acts as an indirect indicator of the level of oxidative stress and a measure of the efficacy of antioxidant supplementation. Plasma cholinesterase estimation was done by colorimetric method. The change in color of the indicator bromothymol blue caused by the liberated acetic acid from cholinesterase read by spectrophotometer at 620 nm was used to determine the levels of cholinesterase.ResultA decrease in the level of oxidative stress was observed among those supplemented with either alpha lipoic acid alone or along with vitamin C, with a slightly more decrease in oxidative stress in the latter group. A p-value of <0.001 is considered significant statistically. The percentage of the benefit of treatment on supplementation with vitamin C and alpha lipoic acid showed a marked increase in group V (26.9%) cases after supplementation with both in combination.ConclusionThe results provide evidence that the oxidative stress induced by acute amitriptyline poisoning is comparatively decreased by supplementation with antioxidants like alpha lipoic acid and vitamin C, than those only on routine standard treatment.

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HIF-dependent antitumorigenic effect of antioxidants in vivo.

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HIF-dependent antitumorigenic effect of antioxidants in vivo.

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