Flavokawain B induces apoptosis of non-small cell lung cancer H460 cells via Bax-initiated mitochondrial and JNK pathway

被引:32
作者
An, JunXia [1 ]
Gao, YaRong [2 ]
Wang, Jing [1 ]
Zhu, QiYu [2 ]
Ma, YuLing [1 ]
Wu, Jian [2 ]
Sun, Jian [1 ]
Tang, YaXiong [1 ]
机构
[1] Chinese Acad Sci, Chengdu Inst Biol, Chengdu 610041, Sichuan, Peoples R China
[2] SW Jiaotong Univ, Sch Life Sci & Engn, Chengdu, Peoples R China
基金
中国国家自然科学基金;
关键词
Apoptosis; Bax; Flavokawain B; JNK; Lung cancer; Survivin; KAVA CHALCONE; UP-REGULATION; TUMOR-GROWTH; SURVIVIN; INHIBITORS; EXPRESSION; BIM;
D O I
10.1007/s10529-012-0976-6
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Flavokawain B (FKB) possesses strong anti-neoplastic activity against many cancer cells. Here we assessed its antitumor activity and molecular mechanisms in lung cancer H460 cells in vitro. FKB significantly inhibited cell proliferation and caused arrest of the cell cycle G2-M of H460 cells in a dose-dependent manner. FKB also inducted apoptosis, which was associated with cytochrome c release, caspase-7 and caspase-9 activation and Bcl-xL/Bax dys-regulation. FKB significantly down-regulated survivin and XIAP, and the inhibitory effect induced by FKB was greatly attenuated by through over-expression of survivin or Bax(-/-) MEFs. Furthermore, FKB activated the mitogen-activated protein kinases and the JNK inhibitor SP600125 significantly decreased the growth-inhibitory and apoptotic effects of FKB. Together, these results suggest the anti-lung cancer potential of flavokawain B for the prevention and treatment of lung cancer.
引用
收藏
页码:1781 / 1788
页数:8
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