Study On Mechanism Of Apoptosis Of Cancer Cells Induced By Benzotriazole

Benzotriazole compounds have been found to show extensive biological activities, many of them have been developed and used as fungicides, plant growth regulators and medicine,and also have been shown to be able to induce growth inhibition in cancer cells.In present study, we synthesized five bioactive benzotriazole derivatives and their structures were confirmed by means of 1HNMR, IR determination, of which one compound 3-((4-(4'-phenyl) pheny l-lH-l,2,3-triazol-1-yl)methyl)-5-(phenylthio) -4H-1,2,4-trizaol-4-amine (MTMO) was selected. It was demonstrated that MTMO could significantly inhibit proliferation of cultured hepatocarcinoma BEL-7402 cancer cells in a dose- and time-dependent manner. Treatment with MTMO resulted in generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential (△Ψm), DNA fragmentation, and apoptosis in BEL -7402 cells. The results suggested that MTMO-induces cells growth inhibition and apoptosis of BEL -7402 cells may be through modulation of mitochondrial functions regulated by ROS. It seems that collapse of△Ψm prior to intracellular ROS arise during the apoptotic process in our experimental system. However, disruption of mitochondrial membrane potential can further augment ROS production and amplify an apoptotic stimulus. Vc and ROS can slow down the apoptosis which demonstrate that ROS is much important to apoptosis.MTMO also induce obvious growth inhibition in rat breast cancer cells 4T-1. Treatment with MTMO resulted in generation of reactive oxygen species (ROS) and disruption of mitochondrial membrane potential in these cells. Significantly. MTMO could induce obvious growth inhibition and apoptosis in cancer cells, which may be a forceful evidence for anti-cancer of benzotriazole compounds.