Betulin induces reactive oxygen species-dependent apoptosis in human gastric cancer SGC7901 cells.
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.
Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun, 130012, Jilin, China.
Yang
Y
Li
Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun, 130012, Jilin, China.|College of Bioengineering, Dalian University, Dalian, Liaoning, China.
Xiaokang
X
Liu
Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun, 130012, Jilin, China.
Dan
D
Jiang
Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun, 130012, Jilin, China.
Yingjia
Y
Lin
Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun, 130012, Jilin, China.
Yushi
Y
Wang
College of Bioengineering, Dalian University, Dalian, Liaoning, China.
Qing
Q
Li
Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun, Jilin, China. 2660424632@qq.com.
Linlin
L
Liu
Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun, 130012, Jilin, China. yhjin@jlu.edu.cn.
Ying-Hua
YH
Jin
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000094062:Betulinic Acid
D017382:Reactive Oxygen Species; D014315:Triterpenes; C002503:betulin; D000094062:Betulinic Acid
Apoptosis; Bcl-2; Betulin; Gastric cancer; ROS, XIAP