Selective killing of gastric cancer cells by a small molecule targeting ROS-mediated ER stress activation

详细信息    查看全文

• 作者：Peng Zou ; Yiqun Xia ; Tongke Chen ; Junru Zhang ; Zhe Wang ; Wenbo Chen ; Minxiao Chen ; Karvannan Kanchana ; Shulin Yang and Guang Liang
• 刊名：Molecular Carcinogenesis
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：55
• 期：6
• 页码：1073-1086
• 全文大小：7531K
• ISSN：1098-2744

文摘

Gastric cancer is one of the leading causes of cancer mortality in the world. Curcumin is a natural product with multiple pharmacological activities, while its clinical application has been limited by the poor chemical stability. We have previously designed a series of curcumin derivatives with high stability and anticancer potentials. The present study aims to identify the anti-cancer effects and mechanisms of WZ26, an analog of curcumin, in gastric cancer cells. In vitro, WZ26 showed higher chemical stability and much stronger anti-proliferative effects than curcumin, accompanied by dose-dependent induction of cell cycle arrest and apoptosis in gastric cancer cells. Mechanistically, the novel compound WZ26 induced ROS production, resulting in the activation of JNK-mitochondrial and ER stress apoptotic pathways. Blockage of ROS production totally reversed WZ26-induced JNK activation, Bcl-2/Bax decrease, ER stress activation, and final cell apoptosis in SGC-7901 cells. WZ26 also exhibited potent anti-tumor effects in human gastric cancer cell xenograft models. WZ26 could be considered as a potential chemotherapeutic agent for the treatment of advanced gastric cancer. In addition, this study also demonstrated that ROS production could be act as a vital candidate pathway for inducing tumor cell apoptosis by targeting mitochondrial and ER stress-related death pathway.