The cytotoxicity induced by brucine from the seed of Strychnos nux-vomica proceeds via apoptosis and is mediated by cyclooxygenase 2 and caspase 3 in SMMC 7221 cells.
The cytotoxicity induced by brucine from the seed of Strychnos nux-vomica proceeds via apoptosis and is mediated by cyclooxygenase 2 and caspase 3 in SMMC 7221 cells.
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DOI：
10.1016/j.fct.2007.03.004
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发表时间：
2007-09
期刊：
影响因子：
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通讯作者：
Wu Yin;Xukun Deng;Fangzhou Yin;Xiao-Chun Zhang;B. Cai
中科院分区：
文献类型：
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作者：
Wu Yin;Xukun Deng;Fangzhou Yin;Xiao-Chun Zhang;B. Cai
为研究马钱子碱、士的宁、氧化马钱子碱和异士的宁对SMMC-7721细胞的细胞毒作用及其可能机制，采用MET法检测其对SMMC-7721细胞的生长抑制作用。马钱子碱对SMMC-7721细胞的生长抑制作用最强。此外，在倒置显微镜、荧光显微镜和透射电子显微镜下直接观察到，马钱子碱引起SMMC-7721细胞皱缩、膜闭塞、凋亡体形成和核固缩，这些都是典型的凋亡性程序性细胞死亡的特征。此外，流式细胞仪分析表明，马钱子碱通过亚二倍体DNA的形成和磷脂酰丝氨酸外化，呈剂量依赖性地诱导SMMC-7721细胞凋亡。马钱子碱诱导的细胞凋亡部分归因于caspase3的激活和环氧合酶2的抑制，因为caspase3特异性抑制剂z-DEVD-fmk和外源性前列腺素E2都不能完全消除马钱子碱诱导的SMMC 7721细胞的凋亡。综上所述，本研究表明马钱子中的主要生物碱具有抑制SMMC-7721细胞增殖的作用，其中马钱子碱可能通过caspase3和环氧合酶2参与诱导SMMC-7721细胞死亡。
To study the cytotoxicity of four alkaloids: brucine, strychnine, brucine N-oxide and isostrychnine from nux vomica on SMMC 7721 cells and their possible mechanisms, MET assay was used to examine the growth inhibitory effects of these alkaloids. Brucine revealed the strongest growth inhibitory effect on SMMC-7721 cells. Furthermore, as directly observed under an inverted microscope, fluorescent microscope and transmission electronic microscope, brucine caused SMMC-7721 cell shrinkage, membrane blobbing, formation of apoptotic body as well as nucleus condensation, all of which are typical characteristics of apoptotic programmed cell death. In addition, brucine dose-dependently caused SMMC-7721 cells apoptosis via formation of subdipolid DNA and phosphatidylserine externalization, as evidenced by flow cytometry analysis. The brucine-induced apoptosis was partially attributed to the activation of caspase 3 as well as cyclooxygenase 2 inhibition, since neither caspase 3 specific inhibitor, z-DEVD-fmk nor was exogenous addition of prostaglandin E2able to completely abrogate the brucine-induced SMMC 7721 cell apoptosis. In sum, this paper indicate that the major alkaloids present in the seed of Strychnos nux-vomica are effective against SMMC-7721 cells proliferation, among which brucine proceeds SMMC-7721 cells death via apoptosis, probably through the participation of caspase 3 and cyclooxygenase 2.