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Pro‐oxidant Activity of Low Doses of Resveratrol Inhibits Hydrogen Peroxide—Induced Apoptosis
Author(s) -
AHMAD KASHIF ADIL,
CLEMENT MARIEVERONIQUE,
PERVAIZ SHAZIB
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1299.067
Subject(s) - hydrogen peroxide , resveratrol , intracellular , superoxide , chemistry , apoptosis , reactive oxygen species , antioxidant , biochemistry , pro oxidant , dna fragmentation , microbiology and biotechnology , programmed cell death , biology , enzyme
A bstract : 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 pro‐oxidant 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.