Glibenclamide induces apoptosis by activating reactive oxygen species dependent JNK pathway in hepatocellular carcinoma cells

نویسندگان

  • Bin Yan
  • Zhiyong Peng
  • Xiao Xing
  • Chunling Du
چکیده

Glibenclamide (Gli) is a widely employed drug in the treatment of type 2 diabetes and many lines of evidence have described its anti-tumor effects in some neoplasms. The aim of the present study was to investigate the effect of Gli on apoptosis of human hepatocellular carcinoma (HCC) cells and to analyze the underlying pathway involved in this action. Two HCC cell lines, HepG-2 and Huh7 were used as the cell models. We found that Gli treatment significantly inhibited cell viability, induced a significant cell-cycle arrest in G2/M-phase and induced apoptosis in both HepG-2 and Huh7 cells. We further verified that apoptosis induction by Gli was accompanied by increase in ROS levels and activation of the JNK pathway. Scavenging of the intracellular ROS with its blocker N-acetyl-L-cysteine (NAC) could mitigate the Gli-induced apoptosis and JNK activation in the two HCC cell lines. Furthermore, inhibition of JNK pathway by its inhibitor SP100625 effectively reduced Gli-induced apoptosis in HCC cells. In conclusion, Gli treatment significantly induced cell apoptosis by promoting ROS-dependent JNK pathway activation in HCC cells. Gli may be a potential clinical anti-tumor drug for HCC.

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عنوان ژورنال:

دوره 37  شماره 

صفحات  -

تاریخ انتشار 2017