SIGNIFICANT MARINE NATURAL-PRODUCTS IN CANCER-RESEARCH

Tumor promote's and possible cancer chemopreventive agents derived fro m marine organisms are the subjects of this article. Tumor promoters a re agents which cause the development of tumors from initiated cells. Compounds of the lyngbvatoxin and aplysiatoxin classes, which are pote nt activators of protein kinase C, belong to the 12-0-tetradecanovlpho rbol-13-acetate (TPA)-type tumor promoters on mouse skin, whereas paly toxin is a non-TPA type tumor promoter. The okadaic acid class compoun ds, which are potent inhibitors of protein phosphatases-I and -2 A are also non-TPA type tumor promoters. They include four structurally dif ferent types, okadaic acid, calyculin, microcystin; also tautomycin, w hich is not a marine natural product, is included. Okadaic acid induce s tumor formation on the skin and in the glandular stomach, calyculin A promotes mouse-skin tumors, and microcystin-LR causes liver tumors. A new mechanism of tumor promotion, which is applicable to various org ans, is thus provided by compounds belonging to the class of okadaic a cid. By contrast, sarcophytol A inhibits tumor promotion ana carcinoge nesis in various organs. The concept of cancer chemoprevention, define d as the prevention of the occurrence of cancer by administration of o ne or several compounds, and the results with sarcophytol A as a possi ble cancer chemopreventive agent are discussed.