The phenomenon of resveratrol: redefining the virtues of promiscuity

Cancer chemoprevention entails the ingestion of dietary or pharmaceutical agents that can prevent, delay, or reverse the process of carcinogenesis. With support provided by the National Cancer Institute, we have been actively engaged in the systematic discovery and characterization of natural chemopreventive agents. The typical approach involves identifying active crude substances such as extracts derived from terrestrial plants or marine organisms, utilizing in vitro bioassay systems, followed by the isolation of pure active components. As part of this project, an extract obtained from a nonedible Peruvian legume, Cassia quinquangulata Rich. (Leguminosae), was evaluated and found to be active as an inhibitor of cyclooxygenase. The active component was identified as resveratrol. Surprisingly broad spectrum activity was observed, indicative of potential to inhibit carcinogenesis at the stages of initiation, promotion, and progression. This discovery has led to many additional research efforts. There are now around 3,500 papers concerning some aspect of resveratrol action, yet the molecule is unusually promiscuous and specific mechanisms remain elusive. Considering the structural simplicity of this stilbene, the intensity of interest is phenomenal.