Mechanisms of Action of New Antitumor Promoters

Abstract

Sarcophytol A, isolated from the soft coral Sarcophyton glaucum, and (-)epigallocatechin gallate (EGCG), isolated from Japanese green tea leaves, had inhibitory effects on tumor promotion by teleocidin, a tumor promoter of the 12-0-tetra-decanoylphorbol-13-acetate (TPA)-type on mouse skin initiated with 7,12 dimethylbenz(a)anthracene (DMBA) in two-stage carcinogenesis experiments (4,5,17). We called them antitumor promoters. Later it turned out that these antitumor promoters also have inhibitory effects on chemical carcinogenesis in various organs (9,13). Moreover, sarcophytol A and EGCG inhibited tumor promotion by okadaic acid, a tumor promoter of the non-TPA type, on mouse skin (7,8). As for the mechanisms of action of tumor promoters, teleocidin activates protein kinase C, whereas okadaic acid inhibits activities of protein phosphatases 1 and 2A (3,6). Since these two antitumor promoters similarly inhibited tumor promotion of the TPA and non-TPA types, it is of interest to study the mechanisms of action of these compounds at the biochemical level.