Resveratrol as an inhibitor of carcinogenesis

Given the high probability of developing cancer over the period of a normal life span, cancer chemoprevention provides an attractive therapeutic strategy for the delay or reversal of this process. A variety of phytochemicals, such as sulfides, isothiocyanates, glucosinolates, flavonoids, carotenoids, phenols, and diarylhepanoids, are known to mediate chemopreventive responses. Resveratrol, a ubiquitous stilbene found in the diet of human beings (e.g., as a component of grapes and wine), was uncovered by bioassay-guided fractionation and found to mediate cancer chemopreventive activity in a murine model with mechanisms involving various stages of the carcinogenic process. This work spurred a myriad of studies that are summarized in this article. As demonstrated with in vitro and cell culture models, resveratrol functions through a plethora of mechanisms, which can vary from model to model. Results from differential gene expression studies are daunting. Irrespective of the precise mechanism, however, efficacy has been demonstrated in some animal models, and a critical evaluation of resveratrol data relative to the characteristics of a promising cancer chemopreventive agent leads to favorable consideration. Animal studies have shown cancer inhibitory activity in a number of models, including adenoma, skin, breast, colon, esophagus, glioma, intestinal, liver, and neuroblastoma. Biomarkers are known, and ample quantities of compound can be produced. Dietary administration is feasible. Several small-scale human trials are under way, and human intervention trials may follow. As learned by past experience, data from these trials are necessary prior to drawing any conclusions, but the current cancer chemopreventive profile of resveratrol provides promise for widespread use in the future.