摘要：Objective To investigate the anticancer effect of xanthoceraside in vitro and the possible mechanisms involved in the potent antiproliferative effect on human breast cancer MCF-7 cell.Methods The inhibition rate of different tumor cells and human peripheral blood lymphocyte cells was investigated by MTT assay.AO/EB double fluorescent dye staining was used to investigate the morphology changes of MCF-7.The DNA agarose gel electrophoresis was further used to observe the DNA Fragmentation.Flow cytometry was employed to investigate the volume changes,the cell cycle distribution and the mitochondrial membrane potential of MCF-7.The antioxidant N-acetylcysteine(NAC)was chosen to detect the influence on oxidant-stress system of MCF-7 cells.Necrostatin-1 was next chosen to detect the influence on antiproliferative effect of xanthoceraside-treated MCF-7 cells.Results Xanthoceraside could inhibit the proliferation of tumor cells significantly in a dose-dependent manner and it has no cytotoxic effects on human peripheral blood lymphocyte cells in vitro.Cytoplasm vacuole was observed but no significant condense of nuclear chromatin was found,meanwhile,MCF-7 cells were bigger and smear was observed by agarose gel electrophoresis after MCF-7 cells were exposed to xanthoceraside.The cell cycle distribution of MCF-7 was greatly changed after exposure to xanthoceraside with an obvious G1 arrest.The mitochondrial membrane potential showed significant decrease.NAC attenuate the antiproliferative effect of xanthoceraside-treated MCF-7 cells but necrostatin-1 had no effects.Conclusions Xanthoceraside-induced necrosis might be dependent of mitochondria,meanwhile reactive oxygen species(ROS)participated in it.The xanthoceraside-induced MCF-7 cell death might not be the cell necrosis which initiated by Fas/TNFR and must be through RIP1 kinase.

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