Cardiac glycosides from the seeds of Thevetia peruviana and their pro-apoptotic activity toward cancer cells
Cardiac glycosides from the seeds of Thevetia peruviana and their pro-apoptotic activity toward cancer cells
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DOI：
10.1080/10286020.2016.1170814
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发表时间：
2016-01-01
影响因子：
1.7
通讯作者：
Yao, Xin-Sheng
中科院分区：
文献类型：
--
作者：
Cheng, Huo-Yun;Tian, Dan-Mei;Yao, Xin-Sheng
经植物化学研究，分离得到7个强心苷(1-7)，其中包括2个新化合物(1和2)。化合物1对人肺癌细胞系P15、人胃癌细胞系MGC-803、人胰腺癌细胞系SW1990和正常肝细胞系LO2的细胞毒作用表明，化合物1能选择性地抑制癌细胞的增殖，IC50在0.05~0.15mU之间。促凋亡活性表明，化合物1以剂量依赖方式诱导MGC-803癌细胞的凋亡。同时，1作用于MGC-803细胞后，caspase3、9原蛋白表达减少，caspase3、9表达增强，Bax/Bcl2比值升高，呈剂量依赖关系。这意味着1通过参与内在的细胞凋亡途径诱导癌细胞的凋亡。此外，1对MGC-803细胞的细胞周期分布显示，1可使细胞周期停滞于G2/M期。综上所述，本研究提示化合物1可能通过诱导内源性细胞凋亡和细胞周期停滞于G2/M期而显示出抗癌活性。
Phytochemical investigation of the seeds of Thevetia peruviana resulted in the isolation of seven cardiac glycosides (1-7), including two new compounds (1 and 2). Cytotoxicity of them toward cancer cell lines P15 (human lung cancer cell), MGC-803 (human gastric cancer cells), SW1990 (human pancreatic cancer cells), and normal hepatocyte cell LO2 suggested that compound 1 could selectively inhibit the proliferation of cancer cell lines with IC50 from 0.05 to 0.15 mu M. Pro-apoptotic activity revealed that it induced the apoptosis of MGC-803 cancer cells in a dose-dependent manner. Meanwhile, treatment of MGC-803 cancer cells with 1 resulted in diminution of pro-caspases 3 and 9 and activation of caspases 3 and 9, while it increased the Bax/Bcl-2 ratio in a dose-dependent manner. These meant that 1 induced the apoptosis of cancer cells by involving the intrinsic apoptotic pathway. In addition, the cell cycle distribution of MGC-803 cancer cells treated by 1 revealed that it could lead to cell cycle arrest at the G2/M phase. Altogether, this study suggested that compound 1 may exhibit anticancer activity by its capability of induction of intrinsic apoptosis and cell cycle arrest at G2/M phase.