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 B0 (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 A1 (11); two ursanes, brein (12) and uvaol (13); and two lupanes, calenduladiol (14) and heliantriol B2 (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 GI50 values (concentration that yields 50% growth) of mostly less than 6 μM.