Zerumbone suppresses IKKα,Akt,and FOXO1 activation,resulting in apoptosis of GBM 8401 cells

Background: zerumbone,a sesquiterpene compound isolated from subtropical ginger,zingiber zerumbet smith,has been documented to exert antitumoral and anti- inflammatory activities. in this study,we demonstrate that zerumbone induces apoptosis in human glioblastoma multiforme (gbm8401) cells and investigate the apoptotic mechanism. methods. we added a caspase inhibitor and transfected wild-type (wt) ikk and akt into gbm 8401 cells,and measured cell viability and apoptosis by mtt assay and flow cytometry. by western blotting,we evaluated activation of caspase-3,dephosphorylation of ikk,akt,foxo1 with time,and change of ikk,akt,and foxo1 phosphorylation after transfection of wt ikk and akt. results: zerumbone (1050 μm) induced death of gbm8401 cells in a dose-dependent manner. flow cytometry studies showed that zerumbone increased the percentage of apoptotic gbm cells. zerumbone also caused caspase-3 activation and poly (adp-ribose) polymerase (parp) production. n-benzyloxycarbonyl -val-ala-asp- fluoromethylketone (zvad-fmk),a broad-spectrum caspase inhibitor,hindered zerumbone-induced cell death. transfection of gbm 8401 cells with wt ikkα inhibited zerumbone-induced apoptosis,and zerumbone significantly decreased ikkα phosphorylation levels in a time-dependent manner. similarly,transfection of gbm8401 cells with akt suppressed zerumbone-induced apoptosis,and zerumbone also diminished akt phosphorylation levels remarkably and time-dependently. moreover,transfection of gbm8401 cells with wt ikkα reduced the zerumbone-induced decrease in akt and foxo1 phosphorylation. however,transfection with wt akt decreased foxo1,but not ikkα,phosphorylation. conclusion: the results suggest that inactivation of ikkα,followed by akt and foxo1 phosphorylation and caspase-3 activation,contributes to zerumbone-induced gbm cell apoptosis. © 2012 weng et al.; licensee biomed central ltd.