Cinobufagin inhibits tumor growth by inducing intrinsic apoptosis through AKT signaling pathway in human nonsmall cell lung cancer cells
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Guangxin Zhang1, Chao Wang2,3, Mei Sun4, Jindong Li1, Bin Wang1, Chengyan Jin1, Peiyan Hua1, Ge Song1, Yifan Zhang1, Lisa L.H. Nguyen2, Ranji Cui5, Runhua Liu2, Lizhong Wang2, Xingyi Zhang1
1Department of Thoracic Surgery, Second Hospital of Jilin University, Changchun, P.R. China
2Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA
3Department of Integrative Endemic Area, Tongji Hospital of Huazhong University of Science and Technology, Wuhan, P.R. China
4Department of Pathology, Second Hospital of Jilin University, Changchun, P.R. China
5Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, Second Hospital of Jilin University, Changchun, P.R. China
Xingyi Zhang, email: email@example.com
Lizhong Wang, email: firstname.lastname@example.org
Keywords: cinobufagin, non-small cell lung cancer, apoptosis, reactive oxygen species, mitochondrial transmembrane potential
Received: December 07, 2015 Accepted: February 18, 2016 Published: March 3, 2016
The cinobufagin (CB) has a broad spectrum of cytotoxicity to inhibit cell proliferation of various human cancer cell lines, but the molecular mechanisms still remain elusive. Here we observed that CB inhibited the cell proliferation and tumor growth, but induced cell cycle arrest and apoptosis in a dose-dependent manner in non-small cell lung cancer (NSCLC) cells. Treatment with CB significantly increased the reactive oxygen species but decreased the mitochondrial membrane potential in NSCLC cells. These effects were markedly blocked when the cells were pretreated with N-acetylcysteine, a specific reactive oxygen species inhibitor. Furthermore, treatment with CB induced the expression of BAX but reduced that of BCL-2, BCL-XL and MCL-1, leading to an activation of caspase-3, chromatin condensation and DNA degradation in order to induce programmed cell death in NSCLC cells. In addition, treatment with CB reduced the expressions of p-AKTT308 and p-AKTS473 and inhibited the AKT/mTOR signaling pathway in NSCLC cells in a time-dependent manner. Our results suggest that CB inhibits tumor growth by inducing intrinsic apoptosis through the AKT signaling pathway in NSCLC cells.
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