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Caspase-8 preferentially senses the apoptosis-inducing action of NG-18, a gambogic acid derivative, in human leukemia HL-60 cells
Tao Z.2; Zhou Y.1; Lu J.1; Duan W.1; Qin Y.1; He X.2; Lin L.1; Ding J.1
2007
Source PublicationCancer Biology and Therapy
ISSN15558576 15384047
Volume6Issue:5Pages:691-696
Abstract

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 downregulation 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. ©2007 Landes Bioscience.

KeywordAnti-tumor Apoptosis Bcl-2 Caspase-8 Gambogic Acid Hl-60 Ng-18
DOI10.4161/cbt.6.5.3960
URLView the original
Indexed BySCI
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000248259900022
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Cited Times [WOS]:43   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionPersonal research not belonging to the institution
Affiliation1.Shanghai Institute of Materia Medica, Chinese Academy of Sciences
2.Zhejiang Normal University
Recommended Citation
GB/T 7714
Tao Z.,Zhou Y.,Lu J.,et al. Caspase-8 preferentially senses the apoptosis-inducing action of NG-18, a gambogic acid derivative, in human leukemia HL-60 cells[J]. Cancer Biology and Therapy,2007,6(5):691-696.
APA Tao Z..,Zhou Y..,Lu J..,Duan W..,Qin Y..,...&Ding J..(2007).Caspase-8 preferentially senses the apoptosis-inducing action of NG-18, a gambogic acid derivative, in human leukemia HL-60 cells.Cancer Biology and Therapy,6(5),691-696.
MLA Tao Z.,et al."Caspase-8 preferentially senses the apoptosis-inducing action of NG-18, a gambogic acid derivative, in human leukemia HL-60 cells".Cancer Biology and Therapy 6.5(2007):691-696.
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