Cells in cryptophycin-induced cell-cycle arrest are susceptible to apoptosis.
Exposure of murine leukemia L1210 cells to the antitumor antibiotic cryptophycin 52 (C52) led to cell-cycle arrest at the prometaphase/metaphase interface within 18 h, but apoptotic nuclei did not appear until 36 h later. To determine whether accumulation of cells in early metaphase might have delayed the apoptotic process, cells were treated with C52 for 18 h and a photodynamic process was used to initiate the release of mitochondrial cytochrome c. Apoptosis was observed within 60 min, indicating that the slow apoptotic response was not caused by an impaired ability of genomic DNA to undergo endonucleosomal cleavage during cell-cycle arrest induced by cryptophycin 52.
Kessel
D
D
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Luo
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects / Q000473:pathology; D047630:Depsipeptides; D004789:Enzyme Activation; D007700:Kinetics; D007939:Leukemia L1210 / Q000473:pathology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D010447:Peptide Hydrolases / Q000378:metabolism; D010456:Peptides, Cyclic / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002843:Chromatin; D047630:Depsipeptides; D010456:Peptides, Cyclic; C088419:cryptophycin; D010447:Peptide Hydrolases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; C108711:DEVDase