A novel benzotriazole derivative inhibits proliferation of human hepatocarcinoma cells by increasing oxidative stress concomitant mitochondrial damage.
Benzotriazole derivatives have been shown to be able to induce growth inhibition in cancer cells. In the present study, we synthesized bioactive compound, 3-(1H-benzo [d] [1,2,3] triazol-1-yl)-1-(4-methoxyphenyl)-1-oxopropan-2-yl benzoate (BmOB), which is a novel benzotriazole derivative. BmOB displayed anti-proliferative effects on several human tumor cell lines. Human hepatocarcinoma BEL-7402 cell line was selected as a model to illustrate BmOB's inhibition effect and its potential mechanism, since it was the highest susceptible cell line to BmOB. It was shown that treatment with BmOB resulted in generation of reactive oxygen species, disruption of mitochondrial membrane potential (DeltaPsim), and cell death in BEL-7402 cells. BmOB induced cytotoxicity could be prevented by antioxidant vitamin C and mitochondrial permeability transition inhibitor cyclosporine A. cyclosporine A could also protect the BmOB induced collapse of DeltaPsim in BEL7402 cells, while vitamin C did not show similar effects. The results suggest that BmOB could inhibit BEL-7402 cell proliferation, and the cell death may occur through the modulation of mitochondrial functions regulated by reactive oxygen species. It appears that collapse of DeltaPsim prior to intracellular reactive oxygen species arose during the cytotoxic process in our experimental system.
Zhang
Shu-Sheng
SS
College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, China.
Zhang
Hui-Qing
HQ
Li
Di
D
Sun
Li-Hong
LH
Ma
Cui-Ping
CP
Wang
Wei
W
Wan
Jun
J
Qu
Bin
B
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D000975:Antioxidants; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D014230:Triazoles; D016572:Cyclosporine; C012771:benzotriazole; D001205:Ascorbic Acid