Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL
Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL
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DOI：
10.1007/s00204-006-0169-y
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发表时间：
2007-10-01
影响因子：
6.1
通讯作者：
Kuo, Wu-Hsien
中科院分区：
文献类型：
--
作者：
Hsu, Wen-Hsiu;Hsieh, Yih-Shou;Kuo, Wu-Hsien
小檗碱是黄连的主要成分，具有多种药理活性，包括抗炎、促进细胞凋亡和抗癌等潜在作用。丝裂原激活蛋白激酶（MAPK）和活性氧（ROS）可能有助于肿瘤发生和促凋亡功能之间的因果关系。研究小檗碱在人结肠癌细胞凋亡途径中的作用机制。用 50 μM 小檗碱处理 SW620 细胞导致 caspase 3 和 caspase 8 的激活、聚 ADP-核糖聚合酶 (PARP) 的裂解以及细胞色素 c 的释放；而BID和抗凋亡因子c-IAP1、Bcl-2和Bcl-(XL)的表达显着下降。小檗碱诱导的剂量依赖性细胞凋亡伴随着 JNK 和 p38 MAPK 的持续磷酸化以及 ROS 的产生。此外，JNK 和 p38 特异性抑制剂可减轻细胞凋亡的诱导。此外，通过激活 JNK 和 p38 信号模块，在小檗碱诱导的细胞凋亡中，磷酸化 c-Jun、FasL 和 t-BID 的细胞水平增加。 NAC 是 ROS 的清除剂，通过抑制 JNK、p38 和 c-jun 激活以及 FasL 和 t-BID 表达，逆转小檗碱诱导的细胞凋亡效应。这些结果使我们推测小檗碱可能通过激活JNK/p38途径和诱导ROS产生在SW620细胞中发挥凋亡级联作用，为小檗碱诱导人结肠癌细胞的细胞死亡提供新的机制。
Berberine is the major constituent of Coptidis Rhizoma with multiple pharmacological activities, including anti-inflammation, promotion of apoptosis and anticancer potential effect. Mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS) may contribute to the causal relationship between tumorigenesis and pro-apoptotic function. Berberine is studied for the mechanism of its action in apoptotic pathway in human colonic carcinoma cell. Treatment of SW620 cells with 50 mu M berberine resulted in activation of the caspase 3 and caspase 8, cleavage of poly ADP-ribose polymerase (PARP) and the release of cytochrome c; whereas, the expression of BID and anti-apoptosis factor c-IAP1, Bcl-2, and Bcl-(XL) were decreased markedly. Berberine-induced, dose-dependent induction of apoptosis was accompanied by sustained phosphorylation of JNK and p38 MAPK, as well as generation of the ROS. Furthermore, the induction of apoptosis was alleviated by inhibitors specific for JNK and p38. In addition, there was an increase in the cellular levels of phospho-c-Jun, FasL and t-BID in the berberine-induced apoptosis via the activation of JNK and p38 signaling modules. NAC administration, a scavenger of ROS, reversed berberine-induced apoptosis effects via inhibition of JNK, p38 and c-jun activation, and FasL and t-BID expression. These results leads us to speculate that berberine may play an apoptotic cascade in SW620 cells by activation of the JNK/p38 pathway and induction of ROS production, providing a new mechanism for berberine-induced cell death in human colon cancer cells.