Molecular mechanisms of the chemopreventive effects of resveratrol and its analogs in colorectal cancer: key role of polyamines?

Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to exhibit a wide range of biological and pharmacological properties. It has been speculated that dietary resveratrol may act as an antioxidant, promote nitric oxide production, inhibit platelet aggregation, and increase high-density lipoprotein cholesterol and thereby serve as a cardioprotective agent (the so-called "French paradox"). Recently, it was demonstrated that resveratrol can function as a cancer chemopreventive agent, and there has been a great deal of experimental effort directed toward defining this effect. It has been shown that resveratrol and some of its analogues interfere with signal transduction pathways. Thus the activities of various protein kinases are inhibited, the expression of nuclear proto-oncogenes declines, and the activity of ornithine decarboxylase (ODC) is reduced. ODC, which catalyzes the rate-limiting step in the biosynthesis of polyamines, is closely linked with cellular proliferation and carcinogenesis. This review summarizes the recent advances that have provided new insights into the molecular mechanisms underlying the promising properties of resveratrol focusing on the key role of the polyamine metabolism in colorectal cancer cells.