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Research Paper
Caspase-8 Preferentially Senses the Apoptosis-Inducing Action of NG-18, A Gambogic Acid Derivative, in Human Leukemia HL-60 Cells
Zhijian Tao, Yunlong Zhou, Jinjian Lu, Wenhu Duan, Xinxia He, Liping Lin and Jian Ding
volume 6 | issue 5
May 2007Pages: 691 - 696
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Gambogic acid (GA) is the major active ingredient of gamboge secreted from a Chinese traditional medicine Garcinia hanburryi possessing potent anti-tumor activity. N-(2-ethoxyethyl)gambogamide (NG-18), a derivative of GA, also efficiently inhibits proliferation of cultured human tumor cells. The inhibition effect of NG-18 is associated with its ability to induce apoptosis. In the present study, NG-18 markedly induced leukemia HL-60 cells apoptosis, and the extrinsic and intrinsic apoptosis pathways were activated almost at the same time. NG-18-induced tumor cell apoptosis was associated with up-regulation of pro-apoptotic Bcl-2 family member Bax, and down-regulation of anti-apoptotic protein Bcl-2. The NG-18-induced apoptosis was blocked completely by a pan-caspase inhibitor Z-VAD-FMK, indicating that caspases were functionally and actively involved in this process. The specific inhibition of caspase-8 activity using Z-IETD-FMK significantly blocked NG-18-induced apoptosis. In contrast, inhibition of other initiator caspases, caspase-2 or -9, using Z-VDVAD-FMK or Z-LEHD-FMK respectively had no effect on NG-18-induced apoptosis. Altogether, our data demonstrated that NG-18-induced apoptosis was dependent on caspases and caspase-8 acted as a key executor in the event.
Authors
Zhijian Tao
Zhejiang Normal University, Zhejiang China
Yunlong Zhou
Chinese Academy of Sciences, Shanghai China
Jinjian Lu
Chinese Academy of Sciences, Shanghai China
Wenhu Duan
Chinese Academy of Sciences, Shanghai China
Xinxia He
Zhejiang Normal University, Zhejiang China
Liping Lin
Chinese Academy of Sciences, Shanghai China
Jian Ding
Chinese Academy of Sciences, Shanghai, China
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.