Hispolon induces apoptosis in human gastric cancer cells through a ROS-mediated mitochondrial pathway
Hispolon induces apoptosis in human gastric cancer cells through a ROS-mediated mitochondrial pathway
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DOI：
10.1016/j.freeradbiomed.2008.03.013
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发表时间：
2008-07-01
影响因子：
7.4
通讯作者：
Li, Yong-Quan
中科院分区：
文献类型：
--
作者：
Chen, Wei;Zhao, Zhao;Li, Yong-Quan
目前胃癌的临床治疗面临着严重的毒副作用和并发症，如胃肠道和血液系统毒性，因此迫切需要寻找新的有效和低毒的治疗方法。Hispolon是一种活性多酚化合物，具有很强的抗菌和抗病毒作用。本研究旨在探讨hispolon对人胃癌细胞的杀伤作用及其机制。Hispolon诱导ROS介导的胃癌细胞凋亡，对胃癌细胞的毒性比对正常胃细胞更大，表明恶性细胞的易感性更高。hispolon诱导胃癌细胞凋亡的机制是通过破坏谷胱甘肽抗氧化系统，引起细胞内大量ROS的积累。过量的ROS引起线粒体膜的氧化损伤，损害膜的完整性，导致细胞色素c的释放，半胱天冬酶激活，和细胞凋亡。此外，hispolon增强了胃癌临床治疗中使用的化疗药物的细胞毒性。这些结果表明，hispolon可能是有用的治疗胃癌作为一个单一的代理或与其他抗癌药物组合。(C)2008年爱思唯尔公司All rights reserved.
Severe side effects and complications such as gastrointestinal and hematological toxicities because of current anticancer drugs are major problems in the clinical management of gastric cancer, which highlights the urgent need for novel effective and less toxic therapeutic approaches. Hispolon, an active polyphenol compound, is known to possess potent antineoplastic and antiviral Properties. In this study, we investigated the efficacy of hispolon in human gastric cancer cells and explored the cell death mechanism. Hispolon induced ROS-mediated apoptosis in gastric cancer cells and was more toxic toward gastric cancer cells than toward normal gastric cells, suggesting greater susceptibility of the malignant cells. The mechanism of hispolon-induced apoptosis was that hispolon abrogated the glutathione antioxidant system and caused massive ROS accumulation in gastric cancer cells. Excessive ROS caused oxidative damage to the mitochondrial membranes and impaired the membrane integrity, leading to cytochrome c release, caspase activation, and apoptosis. Furthermore, hispolon potentiated the cytotoxicity of chemotherapeutic agents used in the clinical management of gastric cancer. These results suggest that hispolon could be useful for the treatment of gastric cancer either as a single agent or in combination with other anticancer agents. (C) 2008 Elsevier Inc. All rights reserved.