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 1′,1′′-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 (IC50: 70 μM) showed much higher (8-fold) antitumour-promoting activity than compound >2 (IC50: 560 μM). In addition, both compounds were nontoxic towards CEM-SS (human T-lymphoblastic leukemia) cells (CD50: >100 μM), Raji (human B-lymphoblastoid) cells (CD50: >600 μM), and brine shrimp (LD50: >300 μM). 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.