Caspase-8 preferentially senses the apoptosis-inducing action of NG-18, a Gambogic acid derivative, in human leukemia HL-60 cells.
Cancer Biol Ther
; 6(5): 691-6, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17426447
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.
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Base de dados:
MEDLINE
Assunto principal:
Medicamentos de Ervas Chinesas
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Apoptose
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Garcinia
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Xantonas
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Proliferação de Células
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Caspase 8
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Antineoplásicos
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article