Induction of apoptosis accompanying with G1 phase arrest and microtubule disassembly in human hepatoma cells by jaspolide B, a new isomalabaricane-type triterpene

Jaspolide B is a novel isomalabaricane-type triterpene isolated from sponge Jaspis sp. We investigated its effects on human hepatoma cells in this study. After 48 It of incubation, jaspolide B inhibited the growth of Bel-7402 and HepG2 cells with IC50 values of 29.1 and 29.5 mu M, respectively. Incubation with 0.5 mu M of jaspolide B caused time-dependent induction of apoptosis in up to 66.8% of Bel-7402 cells for 48 h, and the induction of apoptosis was confirmed by the enhancement of mitochondrial masses and cell membrane permeability, and nuclear condensation in Bel-7402 and HepG2 cells. Moreover, jaspolide B arrested cell cycle progression at G(1) phase of human hepatoma cells in a dose- and time-dependent manner. In addition, treatment of the compound caused dose-dependent disassembly of microtubule cytoskeleton in Bel-7402 cells at indicated concentrations, and this effect being similar but weaker than that of colchicine, a well-known microtubule-disassembly agent. We conclude that the anti-cancer effect of jaspolide B relates to the apoptosis induction, cell cycle arrest and microtubule disassembly, and these multiple mechanisms of jaspolide B, especially the induction of apoptosis, open interesting perspectives for further exploration of the isomalabaricane-type terpenes and compounds of marine sponge origin as potential anticancer agents. (D 2007 Elsevier Ireland Ltd. All rights reserved.