Induction of apoptosis in human leukemia cells by the CDK1 inhibitor CGP74514A.
作者： Paul Dent , Yun Dai , Steven Grant
DOI:
关键词: Apoptosis 、 Cell cycle 、 Poly ADP ribose polymerase 、 Cell culture 、 Biology 、 Dephosphorylation 、 Molecular biology 、 Cyclin-dependent kinase 1 、 Ectopic expression 、 Cytochrome c
摘要: We have examined the effects of CDK1 inhibitor CGP74514A on cell cycle- and apoptosis-related events in human leukemia cells. An 18-hr exposure to 5 ∝M induced mitochondrial damage (i.e., loss ∆ψ m ) apoptosis multiple lines (e.g., U937, HL-60, KG-1, CCRF-CEM, Raji, THP; range 30-95%). In U937 cells, CGP74514A- (5 ∝M) became apparent within 4 hr approached 100% by 24 hr. The pan- caspase Boc-fmk caspase-8 IETD-fmk opposed CGP74514A-induced caspase-9 activation PARP degradation, but not cytochrome c or Smac/DIABLO release. CGP74514A-mediated was substantially blocked ectopic expression full-length Bcl- 2, a loop-deleted mutant Bcl-2, Bcl-x L . treatment ∝M; 18 hr) resulted increased p21 CIP1 expression, p27 KIP1 diminished E2F1 dephosphorylation p34 cdc2 It also early 2 inhibition activity pRb, followed pRb did block phosphorylation at CDK2- CDK4- specific sites. These findings indicate that selective inhibitor, CGP74514A, induces complex changes cycle-related proteins cells accompanied extensive damage, activation, apoptosis.
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