Document Detail

Characterization of adriamycin-induced G2 arrest and its abrogation by caffeine in FL-amnion cells with or without p53.
MedLine Citation:
PMID:  11120603     Owner:  NLM     Status:  MEDLINE    
We investigated the effect of Adriamycin on FL-amnion (FL) cells. After treatment with the drug, the cells arrested at G2, but we did not detect an increase in the p21 levels. We established a p53-deficient derivative of these cells, in which G2 arrest also occurred after treatment with Adriamycin, suggesting that the arrest we observed in these cells is independent of the p53 pathway. Low doses of Adriamycin (100-200 ng/ml) induced G2 arrest, while late S-phase arrest was observed at high doses (500-1000 ng/ml) in both FL and p53-deficient FL cells. Accumulation of cyclin B1 was detected only in cells arrested at G2, and not in those arrested at S phase, suggesting that the S-phase checkpoint functioned efficiently even in p53-deficient FL cells. In both cell lines, caffeine-induced activation of CDC2 kinase was detected only in cells arrested at G2 and CDC2 kinase-activated cells died exhibiting features of apoptosis. CDC2 kinase activation was inhibited by cycloheximide. Furthermore, cycloheximide inhibited activation of CDK2:cyclin A, which normally precedes CDC2 kinase activation in caffeine-treated cells. These results suggest that p53 and p21 do not have special roles in the S- and G2-phase checkpoints and that CDK2:cyclin A could be the target of the G2-phase DNA damage checkpoint.
Y Minemoto; J Gannon; M Masutani; H Nakagama; T Sasagawa; M Inoue; Y Masamune; K Yamashita
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Experimental cell research     Volume:  262     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-01-29     Completed Date:  2001-02-15     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  37-48     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Department of Life Science, Graduate School of Natural Science and Technology, Kanazawa University, Japan.
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MeSH Terms
Amnion / drug effects*,  metabolism
CDC2 Protein Kinase / metabolism
Caffeine / pharmacology*
Cyclin B / metabolism
Cyclin B1
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / metabolism,  physiology*
Cycloheximide / pharmacology
DNA Damage
Doxorubicin / pharmacology*
Enzyme Activation
G2 Phase
Oncogene Proteins, Viral / genetics
Phosphodiesterase Inhibitors / pharmacology*
Protein Synthesis Inhibitors / pharmacology
Repressor Proteins*
S Phase
Signal Transduction / drug effects*
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / metabolism,  physiology*
Reg. No./Substance:
0/CCNB1 protein, human; 0/CDKN1A protein, human; 0/Cyclin B; 0/Cyclin B1; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/E6 protein, Human papillomavirus type 16; 0/Oncogene Proteins, Viral; 0/Phosphodiesterase Inhibitors; 0/Protein Synthesis Inhibitors; 0/Repressor Proteins; 0/Tumor Suppressor Protein p53; 23214-92-8/Doxorubicin; 58-08-2/Caffeine; 66-81-9/Cycloheximide; EC Protein Kinase

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