一种含硒鬼臼衍生物通过引起线粒体膜电位下降诱导SMMC-7721细胞凋亡

目的]为从植物中提取和开发新药提供依据。方法]研究含硒鬼臼衍生物4′-去甲基-4-脱羟基-4-硒代-对甲苯基-β-表鬼臼毒素(SEP)对SMMC-7721细胞凋亡的诱导,并分析SMMC-7721细胞线粒体膜电位的变化。结果]SEP可抑制SMMC-7721的增殖,且有明显的剂量效应。经SEP处理后,SMMC-7721细胞形态明显改变,出现了皱缩、变小等疑似凋亡的特征。M30抗体检测表明SMMC-7721细胞凋亡率随SEP浓度的增加而增加,证实SEP可诱导SMMC-7721细胞凋亡。低浓度SEP(10、20μmol/L)可使SMMC-7721细胞阻滞在G2/M期,而40μmol/LSEP则使阻滞在S期的细胞数明显升高,说明细胞DNA发生了损伤,这很可能引起线粒体凋亡途径的产生。不同浓度SEP处理均可使SMMC-7721细胞线粒体膜电位的下降。结论]SMMC-7721细胞凋亡可能是通过线粒体途径产生的。

SMMC-7721Cell Apoptosis Induced by a Kind of Se-containing Podophyllotoxin Derivative through Causing the Decline of Mitochondrial Membrane Potential

Objective] The aim of the research was to provide the basis for extracting and developing new medicines from plants.Method] The induction of a kind of Se-containing podophyllotoxin derivative 4′-demethyl-4dehydroxy-4-seleno-p-tolyl-β-epipodophyllotxin(SEP) on SMMC-7721cell apoptosis were studied.And the changes of the mitochondrial membrane potential in SMMC-7721cell were analyzed.Result] SEP could inhibit the proliferation of SMMC-7721cells,with an obvious dose effect.After treatment with SEP,the morphology of SMMC-7721cells changed obviously and such suspected apoptosis characteristics as crinkling and lessening appeared.The detection by M30 antibody showed that the apoptosis rate of SMMC-7721cells were increased with the increasing of SEP concn.,which proved that SEP could induce SMMC-7721cell apoptosis.Low-concn.SEP(10,20 μmol/L) could make SMMC-7721cells hindered in G2/M periods and 40 μmol/L SEP made the number of the cells hindered in S period increased obviously,which indicated cell DNA was damaged and this probably caused the production of mitochondria apoptosis pathway.Treatment with different concn.of SEP could make the mitochondrial membrane potential of SMMC-7721cell decline.Conclusion] SMMC-7721cell apoptosis was probably produced through mitochondrial pathway.