Cancer chemopreventive activity of serratane-type triterpenoids on two-stage mouse skin carcinogenesis

Eleven serratane-type triterpenoids isolated from the stem bark of Picea jezoensis (Sieb. et Zucc.) Carr. var. jezoensis (Pinaceae) and the stem bark of Picea jezoensis (Sieb. et Zucc.) Carr. var. hondoensis (Mayer) Rehder (Pinaceae) and three synthetic analogs were studied for their possible inhibitory effects on Epstein–Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). 21-Episerratenediol, serratenediol, diepiserratenediol, 3β-hydroxyserrat-14-en-21-one, 3α-methoxy-21β-hydroxyserrat-14-en-16-one, 3β-methoxyserrat-14-en-21β-yl acetate, 3α-methoxyserrat-14-en-21β-yl acetate and 3β-methoxyserrat-14-en-21α-yl acetate demonstrated strong inhibitory effects on the EBV-EA activation without showing any cytotoxicity, their effects being stronger than that of a representative control, oleanolic acid. Furthermore, 21-episerratenediol exhibited a remarkable inhibitory effect on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene as an initiator and TPA as a promoter. The result of the present investigation indicated that 21-episerratenediol might be valuable as a potent cancer chemopreventive agent.