AS602868, a pharmacological inhibitor of IKK2, reveals the apoptotic potential of TNF-α in Jurkat leukemic cells
C Frelin, V Imbert, E Griessinger, A Loubat, M Dreano… - Oncogene, 2003 - nature.com
C Frelin, V Imbert, E Griessinger, A Loubat, M Dreano, JF Peyron
Oncogene, 2003•nature.comNF-κB 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-α-induced NF-κB activation
in Jurkat leukemic T cells. While TNF-α 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 …
antiapoptotic genes. Pharmacological blockade of the IKK2 kinase with AS602868, a
specific inhibitor that competes with ATP binding, prevented TNF-α-induced NF-κB activation
in Jurkat leukemic T cells. While TNF-α 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 …
Abstract
NF-κB 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-α-induced NF-κB activation in Jurkat leukemic T cells. While TNF-α 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-α+ AS602868. Quantitative real-time PCR demonstrated that AS602868 prevented TNF-α 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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