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

• Main Authors: Weng Hsing-Yu, Hsu Ming-Jen, Wang Ching-Chung, Chen Bing-Chang, Hong Chuang-Ye, Chen Mei-Chieh, Chiu Wen-Ta, Lin Chien-Huang
• Format: Article
• Language: English
• Published: BMC 2012-10-01
• Series: Journal of Biomedical Science
• Subjects: Zerumbone; IKK; Akt; FOXO1; Glioblastoma multiforme
• Online Access: http://www.jbiomedsci.com/content/19/1/86

<p>Abstract</p> <p>Background</p> <p>Zerumbone, a sesquiterpene compound isolated from subtropical ginger, <it>Zingiber zerumbet</it> 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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>Zerumbone (10∽50 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. <it>N</it>-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.</p> <p>Conclusion</p> <p>The results suggest that inactivation of IKKα, followed by Akt and FOXO1 phosphorylation and caspase-3 activation, contributes to zerumbone-induced GBM cell apoptosis.</p>