RESUMO
BACKGROUND & OBJECTIVE: Asiaticoside (ATS), a triterpene extracted from Centella asiatica (L.) Urban, a traditional Chinese herb, possesses good wound healing activities because of its stimulative effect on collagen synthesis. Recently, the anti-tumor effect of asiaticiside has been reported. This study was to examine the induction of apoptosis in cancer cells, and the enhancement of vincristine (VCR) cytotoxicity by asiaticoside. METHODS: MTT assay was used to evaluate inhibitory effect of asiaticoside combined with vincristine on proliferation of several cancer cell lines, including KB, KBv200, MCF-7, and MCF-7/ADM. Cell cycle, and apoptosis of KB cells were analyzed by flow cytometry; apoptosis induction was also proved by electrophoresis,and morphologic assessment; the expression of apoptosis-, and cell cycle-related proteins were determined by Western blot. RESULTS: The IC(50) values of asiaticoside for KB, KBv200, MCF-7, and MCF-7/ADM cells detected by MTT assay were (1.11+/-0.13) mg/ml, (1.82+/-0.08) mg/ml, (1.58+/-0.15) mg/ml, and (3.25+/-0.46) mg/ml, respectively. Multidrug resistant KBv200, and MCF-7/ADM cancer cells displayed similar sensitivity to asiaticoside as their parental counterparts (KB, and MCF-7 cells). Moreover, asiaticoside induced apoptosis in KB cells. At sub-cytotoxicity concentration, asiaticoside showed synergistic effect with vincristine in these 4 cell lines. The apoptosis rates were much higher in asiaticoside plus vincristine groups than in vincristine or asiaticoside groups. Bcl-2 phosphorylation levels were higher in the combination groups than in vincristine or asiaticoside alone groups. The activated caspase-3 protein was only presented in the combination groups. Asiaticoside plus vincristine enhanced S-G(2)/M arrest, up-regulated Cyclin B1 protein expression, and down-regulated P34(cdc2) protein expression in KB cells. CONCLUSION: Asiaticoside, as a biochemical modulator, may induce apoptosis,and enhance anti-tumor activity of vincristine in cancer cells, might be useful in cancer chemotherapy.
