Bax/Bcl-2 and caspase 3 pathway-mediated apoptosis induced by gentiopicroside in human colorectal cancer cells.

e15665 Background: Colorectal cancer (CRC) is one common malignant disease with poor prognosis. Gentiopicroside, main compound in Gentiana and Cephalaria plants, has been reported that it can effect cell proliferation or apoptosis in some tumors. But its influence and mechanism on CRC are not clear yet. Based on our primary study, we tried to figure out the possible effects of gentiopicroside in human CRC cells. Methods: Cell apoptosis was investigated through cell proliferation assay, cell growth curve and clone formation assay in HCT116 cells. The morphological change and apoptosis rate were estimated by Hoechst 33258. Apoptosis via the Bax/Bcl2 and caspase 3 pathway induced by gentiopicroside were also detected by RT-PCR and Western-blot. Furthermore, the level of Bax/Bcl2 and caspase 3 pathway were detected by RT-PCR and Western-blot in through transplanting CRC cells into BALB/c nude mice. Results: MTT assay and Trypan blue staining showed that gentiopicroside reduced HCT116 cells proliferation and clone formation ability. Hoechst 33258 staining also showed that gentiopicroside induced cells apoptosis. Moreover, in nude mice groups, gentiopicroside induced lighter body weight, slower tumor growth speed, and smaller volume and lighter tumor weight. After treated with gentiopicroside, levels of Bax and caspase 3 were increased, and the level of Bcl2 was reduced by in vitro cell culture. Furthermore, gentiopicroside increased levels of Bax and caspase 3 and inhibited the level of Bcl2, which subsequently induced apoptosis via the Bax/Bcl2 and caspase 3 pathway in vivo. Conclusions: Gentiopicroside induced apoptosis through the Bax/Bcl2 and caspase 3 pathway in HCT116 cells. Our study suggests that gentiopicroside has cytotoxic effect on colorectal cancer cells via the induction of apoptosis and in vitro and in vivo.