Antiproliferative activity of Alisol B in MDA-MB-231 cells is mediated by apoptosis, dysregulation of mitochondrial functions, cell cycle arrest and generation of reactive oxygen species
Antiproliferative activity of Alisol B in MDA-MB-231 cells is mediated by apoptosis, dysregulation of mitochondrial functions, cell cycle arrest and generation of reactive oxygen species
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DOI：
10.1016/j.biopha.2016.12.088
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发表时间：
2017-03-01
影响因子：
7.5
通讯作者：
Zou, Mingchang
中科院分区：
文献类型：
--
作者：
Zhang, Aifeng;Sheng, Yuqing;Zou, Mingchang
以往的研究表明，泽泻醇B具有抑制癌细胞的活性。然而，实现抑制的确切机制仍然知之甚少。在本研究中，作者研究了泽泻醇B在人乳腺癌细胞中的作用。泽泻醇B在MDA-MB-231细胞中显示出显著的抗癌活性。结果表明，泽泻醇B的细胞毒性作用是通过诱导细胞凋亡、线粒体膜电位降低、细胞周期阻滞、半胱氨酸天冬氨酸蛋白酶激活和活性氧积累等途径实现的。有趣的是，用一般半胱天冬酶抑制剂z-VAD-FMK预处理细胞显著防止Alisol B诱导的细胞凋亡。Western blot分析显示p-p38表达上调，p-AKT、p-p65和p-mTOR表达下调。综上所述，上述结果表明，泽泻醇B抑制MDA-MB-231细胞的生长主要是通过诱导细胞凋亡;这一结果可能代表了泽泻醇B介导的细胞凋亡的主要机制。(C)2016 Elsevier Masson SAS。All rights reserved.
Previous studies have demonstrated that Alisol B has inhibitory activity in cancer cells. However, the exact mechanism through which inhibition is achieved is still poorly understood. In the present study, the authors examined the effects of Alisol B in human breast cancer cells. Alisol B showed significant anticancer activity in MDA-MB-231 cells. The results demonstrated that the cytotoxicity induced by Alisol B was mediated by induction of apoptosis, decrease in mitochondrial membrane potential, cell cycle arrest, activation of caspases and accumulation of ROS (reactive oxygen species) level. Interestingly, pretreatment of cells with the general caspase inhibitor z-VAD-FMK significantly prevented Alisol B-induced apoptosis. Furthermore, western blot analysis revealed the upregulation of p-p38 and downregulation of p-AKT, p-p65 and p-mTOR. Taken together, the above results suggest that Alisol B suppresses the growth of MDA-MB-231 cells mainly through induction of apoptosis; this outcome may represent the major mechanism of Alisol B-mediated apoptosis. (C) 2016 Elsevier Masson SAS. All rights reserved.