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Cancer Chemopreventive Agents Discovered by Activity-Guided Fractionation: A Review



We currently describe a programmatic effort to discover novel natural product cancer chemopreventive agents, i.e., agents capable of preventing, inhibiting or reversing the process of carcinogenesis. Employing a panel of bioassays reflective of modulating carcinogenesis at the stages of initiation, promotion or progression, and a mouse mammary organ culture model as a secondary discriminator, promising plant extracts are identified and subjected to activity guided fractionation schemes. This report lists 70 active compounds obtained from 22 plants, 14 of which are structurally novel. The isolates represent 16 major plant secondary metabolite compound classes, comprising alkaloids, aryl polysulfides, a benzenoid, diterpenoids, flavonoids, furocoumarins, lignans, a monoterpenoid, rotenoids, quinones, simaroubolides, stilbenoids, a sterol glycoside, triterpenoids, withanolides, and a xanthone. These compounds mediate a variety of biological effects that are consistent with cancer chemoprevention and thus far deguelin and resveratrol have been found active in full-term tumor inhibition studies with laboratory animals. Several other isolates are being produced on larger scales to permit animal testing, and some semi-synthetic leads (based on natural product isolates) have demonstrated promising activities. The program is ongoing, focusing to a greater extent on dietary materials, with the long-term objective of providing nontoxic substances useful for the prevention of cancer in humans.
