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 prevent ing, inhibiting or reversing the process of carcinogenesis. Employing a panel of bioassays reflective of modulating carcinogenesis at the st ages of initiation, promotion or progression, and a mouse mammary orga n 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 s econdary metabolite compound classes, comprising alkaloids, aryl polys ulfides, 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 laborato ry animals. Several other isolates are being produced on larger scales to permit animal testing, and some semi-synthetic leads (based on nat ural product isolates) have demonstrated promising activities. The pro gram is ongoing, focusing to a greater extent on dietary materials, wi th the long-term objective of providing nontoxic substances useful for the prevention of cancer in humans.