β-Elemene inhibits Hsp90/Raf-1 molecular complex inducing apoptosis of glioblastoma cells

被引:61
|
作者
Zhao, Yong-Shun [1 ]
Zhu, Ting-Zhun [1 ]
Chen, Yan-Wei [2 ]
Yao, Yi-Qun [1 ]
Wu, Chun-Ming [1 ]
Wei, Zhen-Qing [1 ]
Wang, Wei [3 ]
Xu, Ying-Hui [1 ]
机构
[1] Dalian Med Univ, Dept Neurosurg, Affiliated Hosp 1, Dalian 116011, Peoples R China
[2] Dalian Med Univ, Dept Clin Pharm, Affiliated Hosp 1, Dalian 116011, Peoples R China
[3] Chinese Acad Sci, Lab Biomed Mat Engn, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
关键词
beta-Elemene; Hsp90/Raf-1; MAPK; Apoptosis; Glioblastoma cell; IN-VITRO; MITOCHONDRIA; PATHWAY; HSP90; RAF-1; BCL-2; ERK; COMBINATION; CARCINOMA; SURVIVAL;
D O I
10.1007/s11060-011-0770-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
beta-Elemene, an active component of herb medicine Curcuma wenyujin, has been shown to antagonize glioblastoma cells by inducing apoptosis. However, how beta-elemene induces apoptosis of these cells remains unclear. In this study, we report that beta-elemene disrupted the formation of the Hsp90/Raf-1 complex, a key step in maintaining the conformation stability of Raf-1, and caused deactivation of Raf-1 and inhibition of the ERK pathway, thereby leading to apoptosis of glioblastoma cells. Specifically, treatment of glioblastoma cell lines with beta-elemene attenuated phosphorylation of multiple members of the kinase families in the Ras/Raf/MEK/ERK cascade, including Raf-1 and ERK as well as downstream signaling targets such as Bcl-2. These results suggest that the Hsp90/Raf-1 complex could be a promising molecular target for new drug development for the treatment of glioblastoma.
引用
收藏
页码:307 / 314
页数:8
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