1-Deoxynojirimycin Derivative Containing Tegafur Induced HCT-116 Cell Apoptosis through Mitochondrial Dysfunction and Oxidative Stress Pathway

文献类型： 外文期刊

第一作者： Tang, Liqing

作者： Tang, Liqing;Xu, Yixing;He, Jianglong;Jiang, Xueping;Li, Yuqi;Li, Hao;Zhang, Ran;Gui, Zhongzheng;Huang, Gaiqun;Li, Hao;Zhang, Ran;Gui, Zhongzheng

作者机构：

关键词： 1-deoxynojirimycin; cell apoptosis; DNA damage; mitochondrial dysfunction; oxidative stress

期刊名称：ACS MEDICINAL CHEMISTRY LETTERS （ 影响因子：4.0； 五年影响因子：4.0 ）

ISSN： 1948-5875

年卷期： 2024 年 15 卷 11 期

页码：

收录情况： SCI

摘要： Three 1-deoxynojirimycin (DNJ) derivatives (named C4-C6) including DNJ and tegafur (TGF) were designed and synthesized, and their antiproliferative effects were investigated. C4-C6, especially C6, exerted good lipophilicity, alpha-glucosidase inhibitory activity, and antitumor effects. Mechanism studies indicated that C6 significantly induced cell apoptosis and S-phase block and inhibited migration of HCT-116 cells. Besides, C6 induced mitochondrial damage by decreasing the mitochondrial membrane potential, improving the accumulation of ROS, upregulating the expression of Bax, and downregulating Bcl-2. Moreover, C6 induced excessive production of ROS to trigger oxidative stress, resulting in an increase in the level of MDA and NO, a decrease in the content of GSH and SOD, and an overexpression of Nrf2. Furthermore, C6 induced DNA damage by down-regulating the expression of thymidylate synthase. These results indicated that C6 is a potential antitumor agent and kills HCT-116 cells through DNA damage, mitochondrial dysfunction, and oxidative stress.

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