Noncytotoxic and Antitumour-Promoting Activities of Garcinia Acid Esters from Garcinia atroviridis Griff, ex T. Anders (Guttiferae)

摘要

The in vitro antitumour-promoting, cytotoxic, and antioxidant activities of two ester derivatives of garcinia acid, that is, 2-(butoxycarbonylmethyl)-3-butoxycarbonyl-2-hydroxy-3-propanolide (1) and l',l"-dibutyl methyl hydroxycitrate (2), that had been previously isolated from the fruits of Garcinia atroviridis Griff, ex T. Anders (Guttiferae), were examined. Based on the inhibition of Epstein-Barr virus early antigen (EBV-EA) activation, compound 1 (IC_(50): 70 muM) showed much higher (8-fold) antitumour-promoting activity than compound 2 (IC_(50): 560 muM). In addition, both compounds were nontoxic towards CEM-SS (human T-lymphoblastic leukemia) cells (CD_(50): >100muM), Raji (human B-lymphoblastoid) cells (CD_(50): >600muM), and brine shrimp (LD_(50): >300muM). Although the antitumour-promoting activity of compound 1 is moderate compared with the known antitumour promoter genistein, its non-toxicity suggests the potential of compound 1 and related structures as chemopreventive agents. The weak antioxidant activity displayed by both compounds also suggested that the primary antitumour-promoting mechanism of compound 1 did not involve oxidative-stress quenching.