Discovery of cancer preventive agents from natural products: from plants to prevention

Cancer chemoprevention has traditionally been defined as a dietary or therapeutic approach for the prevention, delay, or reversal of carcinogenesis. We currently expand this definition to include nontoxic applications for patients with established disease. In this context, efficacy can be achieved by selectively altering cell-cycle progression. In the quest for new cancer chemopreventive agents, we have focused on the isolation of natural products as lead molecules, followed by synthetic modification to improve activity. Using biologic response as a guide for fractionation, over 200 active compounds have been identified. Some of the most interesting include brassinin and 4'-bromoflavone as inducers of quinone reductase, deguelin as an inhibitor of ornithine decarboxylase, resveratrol as an inhibitor of cyclooxygenase, and brusatol as an inducer of cellular differentiation. These agents have demonstrated effectiveness in experimental models of carcinogenesis. Further development of these agents as chemopreventive drugs may proceed through the normal regulatory process (eg, 4'-bromoflavone). Alternatively, some natural products may be administered as dietary supplements (eg, resveratrol). In either case, chemoprevention offers great hope in reducing the morbidity and mortality associated with cancer.