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

Three 1-deoxynojirimycin (DNJ) derivatives (named -) including DNJ and tegafur (TGF) were designed and synthesized, and their antiproliferative effects were investigated. -, especially , exerted good lipophilicity, α-glucosidase inhibitory activity, and antitumor effects. Mechanism studies indicated that significantly induced cell apoptosis and S-phase block and inhibited migration of HCT-116 cells. Besides, induced mitochondrial damage by decreasing the mitochondrial membrane potential, improving the accumulation of ROS, upregulating the expression of Bax, and downregulating Bcl-2. Moreover, 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, induced DNA damage by down-regulating the expression of thymidylate synthase. These results indicated that is a potential antitumor agent and kills HCT-116 cells through DNA damage, mitochondrial dysfunction, and oxidative stress.