NATURAL INHIBITORS OF CARCINOGENESIS

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Chemoprevention is a therapeutic method wherein human cancer is prevented or delayed through oral consumption of non-toxic agents capable of inhibiting the process of carcinogenesis. As an integral component of the national effort to defeat cancer, the merit of this approach is intuitively obvious. A variety of potential cancer chemopreventive agents are known, most of which were discovered on an empirical basis. We have assembled a multi-disciplinary team focused on the discovery and characterization of new cancer chemopreventive agents that are natural products or natural product derivatives. As established by ample precedent, terrestrial plants provide broad chemical diversity. Some unique constituents, useful for the treatment of human ailments, cannot be anticipated aside from the experimental process of natural product drug discovery. Starting with well-characterized dietary and non- dietary plant panel of in vitro bioassays indicative of inhibiting major stages of carcinogenesis. Active materials are evaluated in secondary assay systems of greater physiologic complexity, and those active with these secondary discriminators are subjected to bioassay-guided fractionation. Active principles are structurally-defined by physical and spectroscopic methods, evaluated in a broader array of bioassay systems, and considered as candidates for development. As part of this program project, development involves chemical synthesis or large-scale isolation, evaluation of mechanism and structure-activity relationships, and establishment of cancer chemopreventive potential in short- or long-term from the level of the field to the level of structurally- and mechanistically- defined chemical entities of proven therapeutic efficacy. These undertakings require the efforts of five separate projects that are assisted by two core components, and an External Advisory Board. To facilitate utilization of the newly discovered agents for the prevention of human cancers, the long-term objective of this program project, a formal partnership has been instituted with Monsanto Life Sciences. All elements of the program project have proven effective, and we anticipate unabated progress in the future.