Effect of PD98059 and 8-bromo-cAMP, a PKCζ kinase–defective mutant, on DNR-induced cytotoxicity.

(A) U937 cells were left untreated or pretreated in the absence or presence of 250 μM 8-bromo-cAMP for 30 minutes or 50 μM PD98059 for 30 minutes followed by 0.1 μM DNR for 1 hour. Cell viability was determined at 48 hours by MTT assay. (B) C10 and Z4 cells were treated by 0.1 μM DNR for 1 hour. Cell viability was determined at 48 hours by MTT assay. (C) C10 and Z4 cells were treated by 0.1 μM DNR for 1 hour and apoptosis by DAPI staining as described in “ Materials and methods.” All results are mean ± SEM of 3 independent determinations. *P < .01. (D) Cell samples from patients with AML were left untreated or pretreated in the presence of 50 μM PD98059 for 30 minutes followed by 0.1 μM DNR for 1 hour. Apoptotic cells were determined by MGG.