Research Papers:

Cinobufagin inhibits tumor growth by inducing intrinsic apoptosis through AKT signaling pathway in human nonsmall cell lung cancer cells

Guangxin Zhang _, Chao Wang, Mei Sun, Jindong Li, Bin Wang, Chengyan Jin, Peiyan Hua, Ge Song, Yifan Zhang, Lisa L.H. Nguyen, Ranji Cui, Runhua Liu, Lizhong Wang and Xingyi Zhang

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Oncotarget. 2016; 7:28935-28946. https://doi.org/10.18632/oncotarget.7898

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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

Correspondence to:

Xingyi Zhang, email: [email protected]

Lizhong Wang, email: [email protected]

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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