Abstract
BackgroundThe natural plant polyphenol resveratrol present in some foods including grapes, wine, and peanuts, has been implicated in the inhibition, delay, and reversion of cellular events associated with heart diseases and tumorigenesis. Recent work has suggested that the cancer chemoprotective effect of the compound is primarily linked to its ability to induce cell division cycle arrest and apoptosis, the latter possibly through the activation of pro-apoptotic proteins such as Bax.MethodsThe expression, subcellular localization, and importance of Bax for resveratrol-provoked apoptosis were assessed in human HCT116 colon carcinoma cells and derivatives with both bax alleles inactivated.ResultsLow to moderate concentrations of resveratrol induced co-localization of cellular Bax protein with mitochondria, collapse of the mitochondrial membrane potential, activation of caspases 3 and 9, and finally, apoptosis. In the absence of Bax, membrane potential collapse was delayed, and apoptosis was reduced but not absent. Resveratrol inhibited the formation of colonies by both HCT116 and HCT116 bax -/- cells.ConclusionResveratrol at physiological doses can induce a Bax-mediated and a Bax-independent mitochondrial apoptosis. Both can limit the ability of the cells to form colonies.
Highlights
The natural plant polyphenol resveratrol present in some foods including grapes, wine, and peanuts, has been implicated in the inhibition, delay, and reversion of cellular events associated with heart diseases and tumorigenesis
The latter effects may be of particular relevance for the anti-tumorigenic activity of resveratrol [2], not least because the cell cycle/cell death machinery is altered in many tumor cells and the targeting of this machinery by resveratrol opens up the possibility to affect tumor cells and spare normal proliferating tissue
HCT116 cells are responsive to a variety of stresses including DNA damage and spindle disruption, in part owing to the integrity of the wild-type p53 tumor suppressor pathway
Summary
The natural plant polyphenol resveratrol present in some foods including grapes, wine, and peanuts, has been implicated in the inhibition, delay, and reversion of cellular events associated with heart diseases and tumorigenesis. The consensus of the many in vitro- and a limited number of in vivo-studies seems to be that micromolar quantities of the compound can counteract tumor initiation through anti-oxidant activities and the inhibition of enzymatic carcinogen conversion [2,3,4], or counteract tumor promotion through cyclooxygenase and hydroperoxidase inhibition [5,6], but can affect tumor cell proliferation and survival through the inhibition of cell cycle, stimulation of differentiation, and induction of apoptosis [2,3,4] The latter effects may be of particular relevance for the anti-tumorigenic activity of resveratrol [2], not least because the cell cycle/cell death machinery is altered in many tumor cells and the targeting of this machinery by resveratrol opens up the possibility to affect tumor cells and spare normal proliferating tissue. The compound seems to possess some specificity for tumor cells [7]
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