Anti-tumor-promoting activity of diterpenes from Excoecaria agallocha

To search for possible anti-tumor-promoters, we carried out the primary screening of seventeen diterpenes (1-17) isolated from the resinous wood of Excoecaria agallocha (Euphorbiaceae) using an in vitro synergistic assay system. Of these diterpenes, ent-16-hydroxy-3-oxo-13-epi-manoyloxide (5), (13R,14R)-ent-8alpha,13;14,15-diepoxy-13-epi- labda-3beta-ol (8) ent-3beta-hydroxy-15-beyeren-2-one (10) and ent-15-hydroxy-labda-8(17),13E-dien-3-one (14) exhibited significant inhibitory effects on Epstein-Barr virus (EBV) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, 10 exhibited remarkable anti-tumor-promoting activity in vivo on a two-stage carcinogenesis test of mouse tumor using 7,12-dimethylbenz[a]-anthracene (DMBA) as an initiator and TPA as a promoter.