Altered sensitivity of deoxyadenosine-resistant mouse leukemia L1210 cells to apoptosis induced by 7-hydroxystaurosporine.
The deoxyadenosine-resistant mouse leukemia L1210 cell line (Y8) has previously been shown to be more sensitive to apoptosis induced by DNA damaging agents and by protein synthesis inhibitors than the parental wild-type L1210 (WT) cells. These responses occur independently of p53 as both cell lines lack wild-type p53 function. Recent evidence suggests that a serine/threonine kinase is involved in the divergent cellular responses of the WT and Y8 cells. In the present study, the effects of 7-hydroxystaurosporine (UCN-01), a relatively specific serine/threonine kinase inhibitor, were examined in the WT and Y8 cells. Both cell lines were equally sensitive to the growth inhibitory effects of UCN-01. However, the Y8 cells accumulated in G0/G1 and became apoptotic. Apoptosis induced by UCN-01 in the Y8 cells was mediated by a caspase-3-like activity which could be partially blocked by Ac-DEVD-CHO, a caspase-3 inhibitor. UCN-01 did not alter the phosphorylation status of cdc2 nor cyclin B1 and cdc2 protein levels in either cell line.
Somerville
L
L
Department of Biochemistry, Brody Medical Sciences Building 5E-124, Brody School of Medicine, East Carolina University, Greenville, NC 27858-4354, USA.
Cory
J G
JG
D000470:Alkaloids / Q000494:pharmacology*; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002403:Cathepsins / Q000037:antagonists & inhibitors; D002453:Cell Cycle / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology; D019926:Cyclin B / Q000187:drug effects / Q000378:metabolism; D056744:Cyclin B1; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003574:Cytochrome c Group / Q000187:drug effects / Q000378:metabolism; D003839:Deoxyadenosines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D007939:Leukemia L1210 / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012680:Sensitivity and Specificity; D019311:Staurosporine / Q000031:analogs & derivatives; D014407:Tumor Cells, Cultured
C112287:Ac-aspartyl-glutamyl-valyl-aspartyl-aminomethylcoumarin; D000470:Alkaloids; D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; C534700:Ccnb1 protein, mouse; D003374:Coumarins; D019926:Cyclin B; D056744:Cyclin B1; D015853:Cysteine Proteinase Inhibitors; D003574:Cytochrome c Group; D003839:Deoxyadenosines; D004791:Enzyme Inhibitors; D009842:Oligopeptides; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C096429:L 709049; C054852:7-hydroxystaurosporine; D011493:Protein Kinase C; D016203:CDC2 Protein Kinase; D002403:Cathepsins; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D019311:Staurosporine