Anti-Tumor-Promoting Effects of 25-Methoxyporicoic Acid A and Other Triterpene Acids from Poria cocos

Nine new (1, 3, 5, 8, 12, 13, 15, 17, and 18) and nine known (2, 4, 6, 7, 9-11, 14, and 16) lanostane-type triterpene acids and a known diterpene acid (19) were isolated from the epidermis of the sclerotia of Poria cocos. The structures of the new compounds were established as 16 alpha-,27-dihydroxydehyrotrametenoic acid (1), 25-hydroxy-3-epitumulosic acid (3), 16 alpha,25-dihydroxyeburiconic acid (5), 25-methoxyporicoic acid A (8), 26-hydroxyporicoic acid DM (12), 25-hydroxyporicoic acid C (13), poricoic acid GM (15), poricoic acid HM (17), and 6,7-dehydroporicoic acid H (18), on the basis of spectroscopic methods. On evaluation of the nine new and two of the known compounds, 4 and 19, against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, all of the compounds exhibited inhibitory effects, with IC(50) values in the range 187-348 mol ratio/32 pmol TPA. In addition, compound 8 exhibited an inhibitory effect on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Further, 17 compounds, 1-14, 16, 18, and 19, were evaluated for their cytotoxic activity against two human tumor cell lines, HL60 (leukemia) and CRL1579 (melanoma).