p53-independent anisomycin induced G1 arrest and apoptosis in L1210 cell lines.
An L1210 cell line selected for resistance to deoxyadenosine (Y8) has been shown to have barely detectable levels of p53 mRNA and no measurable p53 protein in comparison to the parental mouse wild-type (WT) L1210 cells. We now show that the protein synthesis inhibitors, anisomycin and cycloheximide, arrest WT cells in the G1 phase of the cell cycle and induce apoptosis in Y8 cells via a p53-independent mechanism. There was a decrease in Rb phosphorylation but without the induction of WAF1 protein. Anisomycin treatment activated NF kappa B in the WT cells as early as 0.5 hr after treatment but did not activate NF kappa B in the Y8 cells. Cycloheximide was neither as potent as anisomycin in arresting WT cells at G1 and inducing apoptosis in Y8 cells, nor as potent in decreasing Rb phosphorylation. The finding that caffeine could override the G1 arrest induced by anisomycin and cycloheximide in the WT cells further supports the idea that the effects of anisomycin or cycloheximide on the cell cycle are at the level of cell cycle regulation, and are likely not mediated exclusively through the inhibition of protein synthesis.
He
A W
AW
Department of Biochemistry, East Carolina University, School of Medicine, Greenville, NC 27858-4354, USA.
Cory
J G
JG
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects*; D007939:Leukemia L1210 / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D016160:Retinoblastoma Protein / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
D016328:NF-kappa B; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D002110:Caffeine; D000841:Anisomycin; D003513:Cycloheximide; D017871:Calcium-Calmodulin-Dependent Protein Kinases