Cancer chemoprevention has received major attention in recent years.41 The focus largely has been on determining the efficacy of well-established chemopreventive agents derived from food or assessing analogs in a variety of experimental models. Yet, there appears to be a critical need to identify new efficacious and nontoxic chemopreventive agents. In this chapter, we have described a bioassay-guided fractionation approach for the discovery of new chemopreventive agents from natural products. Using a rational plant selection process and evaluating plant extracts by mechanism-based bioassays followed by fractionation and structural elucidation, we have identified a variety of new chemopreventive agents from approximately 3000 plants. We also have in place a secondary screening system to select agents that show the greatest promise and are targetorgan specific in their actions. Lastly, a stepwise protocol for advancing newly discovered chemopreventive agents to clinical trials is described. Clearly, this approach offers great hope for the eventual control of cancer in human beings.

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