Rotenone Induces Apoptosis in MCF-7 Human Breast Cancer Cell-Mediated ROS Through JNK and p38 Signaling
Rotenone Induces Apoptosis in MCF-7 Human Breast Cancer Cell-Mediated ROS Through JNK and p38 Signaling
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DOI：
10.1002/mc.20583
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发表时间：
2010-02-01
影响因子：
4.6
通讯作者：
Lin, Jen-Kun
中科院分区：
文献类型：
--
作者：
Deng, Yea-Tzy;Huang, Hsiu-Chen;Lin, Jen-Kun
鱼藤酮是线粒体电子传递链复合物I的抑制剂，导致活性氧（ROS）的产生。鱼藤酮已被证明通过诱导多种癌细胞的凋亡来显示抗癌活性。然而，其潜在机制仍未完全了解。在这里，鱼藤酮对人乳腺癌MCF-7细胞显示出很强的生长抑制作用。DNA流式细胞分析、染色质凝聚和聚（adp -核糖）聚合酶（PARP）裂解表明鱼tenone积极诱导MCF-7细胞凋亡。在鱼藤酮诱导的细胞凋亡中，抗凋亡蛋白Bcl-2降低，而凋亡蛋白Bax呈时间依赖性增加。此外，鱼tenone在MCF-7细胞中的处理导致c-jun n-末端激酶（JNK）和p38丝裂原活化蛋白激酶（MAPKs）的激活，以及细胞外信号调节蛋白激酶1/2 （ERK1/2）的失活。JNK和p38 MAPK的药理抑制显示对鱼藤酮诱导的细胞凋亡有显著的保护作用。综上所述，这些结果表明鱼藤酮可能通过ROS和JNK/p38 MAPKs激活诱导MCF-7细胞凋亡。(C) 2009 Wiley-Liss, Inc。
Rotenone is an inhibitor of the mitochondrial electron transport chain complex I, resulting in the generation of reactive oxygen species (ROS). Rotenone has been shown to display anticancer activity through the induction of apoptosis in various cancer cells. However, the underlying mechanism is still not fully understood. Here, rotenone showed a strong growth inhibitory effect against human breast cancer MCF-7 cells. DNA flow cytometric analysis, chromatin condensation, and poly (ADP-ribose) polymerase (PARP) cleavage indicated rotenone actively induced apoptosis in MCF-7 cells. The antiapoptotic protein, Bcl-2, was decreased, whereas the apoptotic protein, Bax, was increased in a time-dependent manner in rotenone-induced apoptosis. Moreover, the treatment of rotenone in MCF-7 cells caused the activation of c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs), and the inactivation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). The pharmacological inhibition of JNK and p38 MAPK revealed significant protection against rotenone-induced apoptosis. Taken together, these results indicate rotenone may induce apoptosis through ROS and JNK/p38 MAPKs activation in MCF-7 cells. (C) 2009 Wiley-Liss, Inc.