PT  - JOURNAL ARTICLE
AU  - Raina, Deepak
AU  - Mishra, Neerad
AU  - Kumar, Shailendra
AU  - Kharbanda, Surender
AU  - Saxena, Satya
AU  - Kufe, Donald
TI  - Inhibition of c-Abl with STI571 Attenuates Stress-Activated Protein Kinase Activation and Apoptosis in the Cellular Response to 1-β-<span class="sc">d</span>-Arabinofuranosylcytosine
AID  - 10.1124/mol.61.6.1489
DP  - 2002 Jun 01
TA  - Molecular Pharmacology
PG  - 1489--1495
VI  - 61
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/61/6/1489.short
4100  - http://molpharm.aspetjournals.org/content/61/6/1489.full
SO  - Mol Pharmacol2002 Jun 01; 61
AB  - The response of myeloid leukemia cells to treatment with 1-β-d-arabinofuranosylcytosine (ara-C) includes activation of the c-Abl protein tyrosine kinase and the stress-activated protein kinase (SAPK). The present studies demonstrate that treatment of human U-937 leukemia cells with ara-C is associated with translocation of SAPK to mitochondria. STI571 (imatinib mesylate), an inhibitor of c-Abl, blocked both activation and mitochondrial targeting of SAPK in the ara-C response. In concert with these effects of STI571, similar findings were obtained in c-Abl–deficient cells. The results further show that STI571 inhibits ara-C–induced loss of mitochondrial transmembrane potential, caspase-3 activation, and apoptosis. These findings demonstrate that STI571 down-regulates c-Abl–mediated signals that target the mitochondria in the apoptotic response to ara-C.