title: β-elemene inhibits proliferation of human glioblastoma cells through the activation of glia maturation factor β and induces sensitization to cisplatin.
abstract: β-elemene, a natural drug extracted from Curcuma wenyujin, strongly inhibits glioblastoma growth. However, the mechanism of β-elemene antitumor action remains unclear. Glia maturation factor β (GMFβ) regulates cellular growth, fission, differentiation and apoptosis. It has been reported that overexpression of GMFβ inhibits the growth of glioblastoma cells and decreases tumor volume. To illustrate the role of GMFβ in the anti-proliferative effect of β-elemene in glioblastoma, U87 cells were treated with β-elemene at various doses and for different periods of time, and levels of phospho-GMFβ (p-GMFβ) and total GMFβ were determined by immunoprecipitation and western blot analysis. Upon GMFβ silencing using RNA interference, the antitumor action of β-elemene was evaluated in a methyl thiazolyl tetrazolium assay and by semi-quantitative western blot analysis of MKK3/6 and p-MKK3/6 expression. Finally, chemosensitization to cisplatin by β-elemene was examined using a cell counting array, and the cell growth inhibitory rate was calculated. The results showed that β-elemene inhibits U87 cell viability through the activation of the GMFβ signaling pathway. Conversely, silencing the expression of GMFβ reversed the antitumor effect of β-elemene and impaired the phosphorylation of MKK3/6. Furthermore, β-elemene increased the sensitivity of U87 glioblastoma cells to the chemotherapeutic agent cisplatin. Taken together, these results suggest that activation of the GMFβ pathway mediates the antitumor effect of β-elemene in glioblastoma. GMFβ is a putative molecular target for glioblastoma therapy.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China.
authors.forename: Tingzhun
authors.initials: T
authors.lastname: Zhu
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Xu
authors.forename: Bin
authors.initials: B
authors.lastname: Dong
authors.forename: Jianing
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Wei
authors.forename: Yousong
authors.initials: Y
authors.lastname: Xu
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Yao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D020904:Glia Maturation Factor / Q000378:metabolism*; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D048371:MAP Kinase Kinase 3 / Q000378:metabolism; D048669:MAP Kinase Kinase 6 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D020904:Glia Maturation Factor; D034741:RNA, Small Interfering; D012717:Sesquiterpenes; C445979:beta-elemene; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6; D002945:Cisplatin