AS602868, a pharmacological inhibitor of IKK2, reveals the apoptotic potential of TNF-alpha in Jurkat leukemic cells.
Oncogene
; 22(50): 8187-94, 2003 Nov 06.
Article
em En
| MEDLINE
| ID: mdl-14603259
ABSTRACT
NF-kappaB transcription factors promote survival in numerous cell types via induction of antiapoptotic genes. Pharmacological blockade of the IKK2 kinase with AS602868, a specific inhibitor that competes with ATP binding, prevented TNF-alpha-induced NF-kappaB activation in Jurkat leukemic T cells. While TNF-alpha by itself had no effect on Jurkat survival, the addition of AS602868 induced cell death, visualized by DNA fragmentation and sub-G1 analysis. A disruption of the mitochondrial potential followed by activation of caspases 9 and 3 was observed in cells treated by the combination TNF-alpha+AS602868. Quantitative real-time PCR demonstrated that AS602868 prevented TNF-alpha induction of the antiapoptotic genes coding for c-IAP-2, Bclx, Bfl-1/A1 and Traf-1. The use of a specific IKK2 inhibitor appears, therefore, as an interesting pharmaceutical strategy to increase the cell's sensitivity towards apoptotic effectors.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia de Células T
/
Fator de Necrose Tumoral alfa
/
Proteínas Serina-Treonina Quinases
/
Apoptose
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article