Fig. 7
Mitochondrial events implicated in CDKs inhibitors-induced apoptosis. a Measurement of mitochondrial membrane potential (MMP, Ψm) variation. K562 or KCL22 cells were treated by 2 μM of the different CDK inhibitors for increasing exposure times and analyzed for MMP variation by DiOC6 incorporation in a flow cytometer. Pretreatment was done with 100 μM z-VAD-fmk pan-caspase inhibitor (ICF) when mentioned. Graph shows results for R-CR8, as a representative for other CDK inhibitors. Results are expressed as Ψm fold increase versus untreated cells for each time point. Each experiment was performed twice. *: ρ < 0.05, **: ρ < 0.01 ***: ρ < 0.001. b Mcl-1 down-regulation assessed by western-blotting on KCL22 cellular extracts. c Subcellular fractions of KCL22 cells treated by 10 μM R-CR8, S-CR8, MR4 or left untreated for 24 h were analyzed by western-blotting for pro- and anti-apoptotic molecules. COX-IV, actin, and NPM were used as control for sample loading for mitochondrial, cytosolic, and nuclear fractions, respectively