ß-Elemene induces apoptosis as well as protective autophagy in human non-small-cell lung cancer A549 cells

被引:55
作者
Liu, Jing [1 ]
Hu, Xue-Jun [2 ]
Jin, Bo [1 ]
Qu, Xiu-Juan [1 ]
Hou, Ke-Zuo [1 ]
Liu, Yun-Peng [1 ]
机构
[1] China Med Univ, Hosp 1, Dept Med Oncol, Shenyang 110001, Peoples R China
[2] China Med Univ, Hosp 1, Dept Resp Med, Shenyang 110001, Peoples R China
关键词
apoptosis; autophagy; ss-elemene; lung cancer; mTOR; BETA-ELEMENE; GLIOBLASTOMA CELLS; MTOR PATHWAY; COLON-CANCER; ARREST; CYCLE; INHIBITION; THERAPY;
D O I
10.1111/j.2042-7158.2011.01371.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Objectives beta-Elemene, a novel traditional Chinese medicine, has been shown to be effective against a wide range of tumours. In this study, the antitumour effect of beta-elemene on human non-small-cell lung cancer (NSCLC) A549 cells and the mechanism involved have been investigated. Methods Cell viability and apoptosis were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein expression was assayed by Western blotting. Autophagy was evaluated under fluorescence microscopy and transmission electron microscopy. Key findings beta-Elemene inhibited the viability of A549 cells in a dose-dependent manner. This suppression of cell viability was due to the induction of apoptosis. Further study showed that beta-elemene inhibited the activity of the PI3K/Akt/mTOR/p70S6K1 signalling pathway, and at the same time it triggered a robust autophagy. The autophagy was characterized by the accumulation of punctate LC3 dots in the cytoplasm, morphological changes, and the increased levels of LC3-II as well as Atg5-Atg12 conjugated proteins. Inhibition of autophagy with chlorochine significantly enhanced the antitumour effect of beta-elemene. Conclusions Our data indicated that beta-elemene inhibited the activity of the PI3K/Akt/mTOR/p70S6K1 signalling pathway in human NSCLC A549 cells, which resulted in apoptosis as well as protective autophagy. A combination of beta-elemene with autophagy inhibitor might be an effective therapeutic option for advanced NSCLC.
引用
收藏
页码:146 / 153
页数:8
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