title: Β-elemene inhibits Hsp90/Raf-1 molecular complex inducing apoptosis of glioblastoma cells.
abstract: β-Elemene, an active component of herb medicine Curcuma wenyujin, has been shown to antagonize glioblastoma cells by inducing apoptosis. However, how β-elemene induces apoptosis of these cells remains unclear. In this study, we report that β-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 β-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.
authors.affiliation: Department of Neurosurgery, 1st Affiliated Hospital of Dalian Medical University, 222 Zhong Shan Road, Dalian 116011, People's Republic of China.
authors.forename: Yong-Shun
authors.initials: YS
authors.lastname: Zhao
authors.forename: Ting-Zhun
authors.initials: TZ
authors.lastname: Zhu
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Chen
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Yao
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Wu
authors.forename: Zhen-Qing
authors.initials: ZQ
authors.lastname: Wei
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000178:diet therapy; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008819:Mice, Nude; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018841:HSP90 Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012717:Sesquiterpenes; D051028:bcl-2-Associated X Protein; C445979:beta-elemene; D019908:Proto-Oncogene Proteins c-raf