Polygonatum cyrtonema lectin induces apoptosis and autophagy in human melanoma A375 cells through a mitochondria-mediated ROS-p38-p53 pathway

Polygonatum cyrtonema lectin induces apoptosis and autophagy in human melanoma A375 cells through a mitochondria-mediated ROS-p38-p53 pathway
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DOI:
10.1016/j.canlet.2008.09.042
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发表时间:
2009-03-08
期刊:
影响因子:
9.7
通讯作者:
Bao, Jin-ku
Bao, Jin-ku
中科院分区:
医学1区
文献类型:
--
作者:
Liu, Bo;Cheng, Yan;Bao, Jin-ku

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黄精凝集素(PCL)是一种甘露糖结合凝集素,具有诱导细胞毒和诱导细胞凋亡的作用。在此,我们证明了PCL诱导A375细胞的凋亡和自噬。其作用机制可能是PCL诱导Bax、Bclxl和Bcl2蛋白表达,导致线粒体去极化、细胞色素c释放和caspase激活。随后,我们发现PCL处理破坏了谷胱甘肽抗氧化系统,诱导线粒体产生ROS积聚,导致p38-P53的激活。此外,我们还证实ROS-p38-P53通路参与了PCL诱导的自噬。综上所述,这些结果表明PCL通过线粒体介导的ROS-p38-P53途径诱导细胞凋亡和自噬。(C)2008爱思唯尔爱尔兰有限公司。保留所有权利。
Polygonatum cyrtonema lectin (PCL), a mannose-binding lectin, has been reported to induce cytotoxicity and apoptosis. Herein, we demonstrated that PCL-induced apoptosis and autophagy in A375 cells. The apoptotic mechanism was that PCL treatment regulated Bax, Bcl-xL and Bcl-2 proteins, leading to mitochondrial depolarization, cytochrome c release and caspase activation. Subsequently, we found that PCL treatment abrogated glutathione antioxidant system and induced mitochondria to generate ROS accumulation, resulting in p38-p53 activation. Moreover, we confirmed that the ROS-p38-p53 pathway was involved in PCL-induced autophagy. In conclusion, these results indicate that PCL induces apoptosis and autophagy via a mitochondrial-mediated ROS-p38-p53 pathway. (C) 2008 Elsevier Ireland Ltd. All rights reserved.