高等学校化学研究 ›› 2010, Vol. 26 ›› Issue (5): 792-797.
Caspase-9 Activation—Critical for Betulin-induced Apoptosis of Human Hepatoma Cells
LI Yang1 , SHEN Jared Taiyi1, GAO Chang1, LI Qing2 and JIN Ying-hua1*
- 1. Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, Jilin University, Changchun 130021, P. R. China;
2. College of Bioengineering, Dalian University, Dalian 116622, P. R. China
Caspase-9 Activation—Critical for Betulin-induced Apoptosis of Human Hepatoma Cells
LI Yang1 , SHEN Jared Taiyi1, GAO Chang1, LI Qing2 and JIN Ying-hua1*
- 1. Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, Jilin University, Changchun 130021, P. R. China;
2. College of Bioengineering, Dalian University, Dalian 116622, P. R. China
摘要： Betulinic acid and its derivatives have been extensively studied in the past for their anti-tumor effects, but relatively little is known about its precursor betulin. In this study we showed that betulin, an abundant natural product, significantly inhibits the cell growth of human hepatoma HepG2 cells in a dose-dependent manner. In the presence of 10 ?g/mL betulin, HepG2 cells undergo an apoptosis, as evidenced by apoptotic morphology such as cell shrinkage, membrane blebbing, nuclear condensation and fragmentation, apoptotic body formation, and caspase activation. Kinetics analysis shows that the depolarization of the mitochondrial membrane potential and the release of the mitochondrial apoptotic protein cytochrome c occurred as early as 2 h post treatment of HepG2 cells with 10 ?g/mL betulin. Proteolytic activation of caspase-9, but not caspase-8, was observed in this apoptosis process. Moreover, the inactivation of caspase-9 by its specific siRNA dramatically reduced betulin-induced caspase-3 activation and apoptosis. Taken together, our observations indicate that the activation of caspase-9 is critical for betulin-induced apoptosis of human hepatoma HepG2 cells.