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Betulin induces reactive oxygen species-dependent apoptosis in human gastric cancer SGC7901 cells
Authors:Yang Li  Xiaokang Liu  Dan Jiang  Yingjia Lin  Yushi Wang  Qing Li  Linlin Liu  Ying-Hua Jin
Institution:1.Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science,Jilin University,Changchun,China;2.College of Bioengineering,Dalian University,Dalian,China;3.Department of Radiation Oncology,The Second Hospital of Jilin University,Changchun,China
Abstract:Betulin, an abundant natural compound, significantly inhibited the cell viability of advanced human gastric cancer SGC7901 cells. Mechanism study demonstrated that betulin induced apoptosis through mitochondrial Bax and Bak accumulation-mediated intrinsic apoptosis pathway. Downregulation of the anti-apoptosis proteins Bcl-2 and XIAP was involved during betulin-induced cell apoptosis. Reactive oxygen species (ROS) was generated in cells after betulin treatment in a time- and dose-dependent manner. Addition of antioxidant N-acetyl-l-cysteine (NAC) significantly attenuated betulin-induced ROS generation as well as Bcl-2 and XIAP downregulation. The mitochondrial accumulation of Bax and Bak, as well as caspase activity, was also remarkably inhibited by NAC treatment, indicating that ROS are important signaling intermediates that lead to betulin-induced apoptosis by modulating multiple apoptosis-regulating proteins in SGC7901 cells.
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