Chang, Cheng

Liu, Shi-quan

Luo, Jun

Mei, Juan-juan

Zhu, You-Qing

Journal of Experimental & Clinical Cancer Research

English

PubMed

Cheng Chang

You-Qing Zhu

Juan-juan Mei

Shi-quan Liu

Jun Luo

Springer - Publisher Connector

Involvement of mitochondrial pathway in NCTD-induced cytotoxicity in human hepG2 cells

Abstract
          
            Background
            Norcantharidin, the demethylated analog of cantharidin derived from a traditional Chinese medicine, Mylabris, has been used in the treatment of anti-cancer effects. However, the detailed mechanisms underlying this process are generally unclear. The aim of this study was to investigate the mechanism of NCTD-induced apoptosis in HepG2 cells.
          
          
            Methods
            The cytotoxicity was measured by MTT assay for cellular viability and by flow cytometry. The mitochondrial membrane potential and reactive oxygen species production was evaluated by flow cytometry analysis. The role of caspase activities were assayed using caspase apoptosis detection kit . Western blot analysis was used to evaluate the level of Cyto-C, Bcl-2, Bax, Bid, caspase 3, -9, -8 and PARP expression
          
          
            Results
            After treatment with NCTD, a decrease in the viability of HepG2 cells and increase in apoptosis were observed. NCTD-induced apoptosis was accompanied by an increase in ROS production, loss of mitochondrial membrane potential and release of cytochrome c(cyto-c) from the mitochondria to the cytosol and down-regulation of anti-apoptotic protein Bcl-2 levels with concurrent up-regulation in pro-apoptotic protein Bax levels. However, another pro-apoptotic molecule, Bid, showed no change in such same treatment. NCTD-increased activity of caspase 9,caspase 3 and the subsequent cleavage caspase substrate PARP were also observed. The expression levels of pro-caspase-8 were not changed after NCTD treatment.
          
          
            Conclusion
            These results indicate that NCTD induced cytotoxicity in HepG2 cells by apoptosis, which is mediated through ROS generation and mitochondrial pathway.
          </jats:sec

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Involvement of mitochondrial pathway in NCTD-induced cytotoxicity in human hepG2 cells

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