Interferonalpha enhances etoposide-induced apoptosis in human osteosarcoma U2OS cells by a p53-dependent pathway.
Life Sci
; 82(7-8): 393-401, 2008 Feb 13.
Article
en En
| MEDLINE
| ID: mdl-18191951
ABSTRACT
Interferonalpha (IFNalpha) induces cell cycle arrest and triggers apoptosis and chemosensitivity. But the mechanism of IFNalpha in regulating chemosensitivity has not been fully understood. To study whether IFNalpha affected chemosensitivity of osteosarcoma cells, we treated p53-wild U2OS cells and p53-mutant MG63 cells with IFNalpha and etoposide, alone or in combination, and then examined growth inhibition, cell cycle arrest and apoptosis. IFNalpha enhanced etoposide-induced growth inhibition and apoptosis in p53-wild U2OS cells but not p53-mutant MG63 cells in a dose- and time-dependent manner. Etoposide-induced G2/M phase arrest was also enhanced by IFNalpha. The enhanced apoptosis was associated with the accumulation of transcriptionally active p53 accompanied with increased Bax and Mdm2, as well as decreased Bcl-2. IFNalpha also activated caspases-3, -8 and -9 protein kinases and PARP cleavage in response to etoposide in U2OS cells. Moreover, the combination-induced cytotoxicity and PARP cleavage were significantly reduced by caspase pan inhibitor and p53 siRNA. Thus we conclude that IFNalpha enhances etoposide-induced apoptosis in human osteosarcoma U2OS cells by a p53-dependent and caspase-activation pathway. The proper combination of IFNalpha and conventional chemotherapeutic agents may be a rational strategy for the treatment of human osteosarcoma with functional p53.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Óseas
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Osteosarcoma
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Proteína p53 Supresora de Tumor
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Interferón-alfa
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Apoptosis
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Etopósido
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Antineoplásicos Fitogénicos
Límite:
Humans
Idioma:
En
Revista:
Life Sci
Año:
2008
Tipo del documento:
Article
País de afiliación:
China