Pro-oxidant Activity of Low Doses of Resveratrol Inhibits Hydrogen Peroxide - Induced Apoptosis

Kashif Adil Ahmad, Marie Veronique Clement, Shazib Pervaiz

Research output: Contribution to journalArticle

Abstract

We have recently shown that efficient apoptotic signaling is a function of a permissive intracellular milieu created by a decrease in the ratio of superoxide to hydrogen peroxide and cytosolic acidification. Resveratrol, a phytoalexin found in grapes and wines, triggers apoptosis in some systems and inhibits the death signal in others. In this regard, the reported inhibitory effect on hydrogen peroxide-induced apoptosis has been attributed to its antioxidant property. Here, we provide evidence that exposure of human leukemia cells to low concentrations of resveratrol (4-8 μM) inhibits caspase activation and DNA fragmentation induced by incubation with hydrogen peroxide or upon triggering apoptosis with a novel compound that kills via intracellular hydrogen peroxide production. At these concentrations, resveratrol elicits pro-oxidant properties as evidenced by an increase in intracellular superoxide concentration. This prooxidant effect is further supported by our observations that the drop in intracellular superoxide and cytosolic acidification induced by hydrogen peroxide is completely blocked in cells preincubated with resveratrol. Thus, the inhibitory effect of resveratrol on hydrogen peroxide-induced apoptosis is not due to its antioxidant activity, but contrarily via a pro-oxidant effect that creates an intracellular environment nonconducive for apoptotic execution.

Original languageEnglish (US)
Pages (from-to)365-373
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume1010
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Keywords

  • Apoptosis
  • Hydrogen peroxide
  • Reductive stress
  • Resveratrol

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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