Constituents of Compositae plants: III. Anti-tumor promoting effects and cytotoxic activity against human cancer cell lines of triterpene diols and triols from edible chrysanthemum flowers

Fifteen pentacyclic triterpene diols and triols, consisting of: six taraxastanes, faradiol ( 1), heliantriol B 0 ( 2), heliantriol C ( 3), 22α-methoxyfaradiol ( 4), arnidiol ( 5), and faradiol α-epoxide ( 6); five oleananes, maniladiol ( 7), erythrodiol ( 8), longispinogenin ( 9), coflodiol ( 10), and heliantriol A 1 ( 11); two ursanes, brein ( 12) and uvaol ( 13); and two lupanes, calenduladiol ( 14) and heliantriol B 2 ( 15), isolated from the non-saponifiable lipid fraction of the edible flower extract of chrysanthemum ( Chrysanthemum morifolium) were evaluated for their inhibitory effects on Epstein–Barr virus early antigen (EBV-EA) activation induced by the tumor promoter, 12- O-tetradecanoylphorbol-13-acetate, in Raji cells as a primary screening test for anti-tumor-promoters. All of the compounds tested showed inhibitory effects against EBV-EA activation with potencies either comparable with or stronger than that of glycyrrhetic acid, a known natural anti-tumor-promoter. Evaluation of the cytotoxic activity of six compounds, 1– 3 and 5– 7, against human cancer cell lines revealed that compound 5 possesses a wide range of cytotoxicity, with GI 50 values (concentration that yields 50% growth) of mostly less than 6 μM.