Berberine-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species generation and mitochondrial-related apoptotic pathway
Berberine-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species generation and mitochondrial-related apoptotic pathway
复制标题
小檗碱诱导的人乳腺癌细胞凋亡是由活性氧生成和线粒体相关凋亡途径介导的。
DOI：
10.1007/s13277-014-2754-7
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发表时间：
2015-02-01
期刊：
影响因子：
--
通讯作者：
Wang, Li
中科院分区：
文献类型：
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作者：
Xie, Juan;Xu, Yinyan;Wang, Li
近年来，小檗碱因其广泛的生物化学和药理作用，包括抗肿瘤作用而受到广泛关注，但其确切机制尚不清楚。用小檗碱处理人乳腺癌细胞（MCF-7和MDA-MB-231细胞）诱导细胞活力以浓度和时间依赖的方式抑制，而不考虑其雌激素受体（ER）的表达。Hoechst33342染色证实小檗碱诱导乳腺癌细胞凋亡呈时间依赖性。由于细胞凋亡诱导被认为是预防和治疗癌症的重要策略，小檗碱可能是一种有效的乳腺癌化疗药物。本研究对小檗碱诱导的人乳腺癌细胞氧化应激及线粒体相关凋亡通路进行了研究。在MCF-7和MDA-MB-231细胞中，小檗碱增加活性氧（ROS）的产生，激活促凋亡的JNK信号。磷酸化JNK触发线粒体膜电位（Delta Im）去极化，下调抗凋亡蛋白Bcl-2的表达，同时上调促凋亡蛋白Bax的表达。抗凋亡Bcl-2家族蛋白的下调与Delta Im的缺失并行，导致线粒体细胞色素c和凋亡诱导因子（apoptosis-inducing factor， AIF）的释放增加，最终触发caspase依赖性和caspase非依赖性凋亡。综上所述，我们的研究揭示了小檗碱通过活性氧生成和线粒体相关凋亡途径在乳腺癌细胞中发挥抗肿瘤活性。这些发现为小檗碱治疗乳腺癌的潜力提供了深入的见解。
Berberine has drawn extensive attention toward their wide range of biochemical and pharmacological effects, including antineoplastic effect in recent years, but the precise mechanisms remain unclear. Treatment of human breast cancer cells (MCF-7 and MDA-MB-231 cells) with berberine induced inhibition of cell viability in concentration- and time-dependent manner irrespective of their estrogen receptor (ER) expression. Hoechst33342 staining confirmed berberine induced breast cancer cell apoptosis in time-dependent manner. Because apoptosis induction is considered to be a crucial strategy for cancer prevention and therapy, berberine may be an effective chemotherapeutic agent against breast cancer. To explore the precise mechanism, berberine-induced oxidative stress and mitochondrial-related apoptotic pathway in human breast cancer cells were investigated in this study. In both MCF-7 and MDA-MB-231 cells, berberine increased the production of reactive oxygen species (ROS), which activated the pro-apoptotic JNK signaling. Phosphorylated JNK triggered mitochondria membrane potential (Delta Im) depolarization and downregulation expression of anti-apoptotic protein Bcl-2 concomitant with the upregulation expression of pro-apoptotic protein Bax. Downregulation of anti-apoptotic Bcl-2 family protein in parallel with loss of Delta Im, leading to increased the release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria, and eventually triggered the caspase-dependent and caspase-independent apoptosis. Taken together, our study reveled that berberine exerted an antitumor activity in breast cancer cells by reactive oxygen species generation and mitochondrial-related apoptotic pathway. These finding provide an insight into the potential of berberine for breast cancer therapy.