- 作者: Hsing-Yu Weng, Ming-Jen Hsu, Ching-Chung Wang, Bing-Chang Chen, Chuang-Ye Hong, Mei-Chieh Chen, Wen-Ta Chiu and Chien-Huang Lin
- 作者服務機構: Graduate Institute of Clinical Medicine, Taipei Medical University, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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 (10[reversed tilde]50 muM) induced death of GBM8401 cells in a dose-dependent manner. Flow cytometry studies show that zerumbone increases the percentage of apoptotic GBM cells. Zerumbone also causes 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 IKK alpha[unknown] inhibited zerumbone-induced apoptosis, and zerumbone significantly decreased IKK alpha[unknown] 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 IKKalpha[unknown] reduced the zerumbone-induced decrease in Akt and FOXO1 phosphorylation.[unknown][unknown]However, transfection with WT Akt decreased FOXO1, but not IKK alpha, phosphorylation.
Conclusion: The results suggest that inactivation of IKK alpha, followed by Akt and FOXO1 phosphorylation and caspase-3 activation, contributes to zerumbone-induced GBM cell apoptosis.
- 中文關鍵字: --
- 英文關鍵字: Zerumbone, IKK, Akt, FOXO1, Glioblastoma multiforme