Document Detail


12-O-tetradecanoylphorbol-13-acetate induces transient cell cycle arrest in G1 and G2 in metastatic melanoma cells: inhibition of phosphorylation of p34cdc2.
MedLine Citation:
PMID:  1390335     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The growth of Demel human metastatic melanoma cells was inhibited by 12-O-tetradecanoylphorbol-13-acetate (TPA) and other nonphorbol tumor promoters including palytoxin and okadaic acid. Using flow cytometry, we have demonstrated that the cells arrested growth in G1 and G2 phases of the cell cycle. Detailed analysis of the kinetics of the growth arrest in unsynchronized cells showed that (a) the growth arrest was transient and peaked 16-20 h following addition of TPA; (b) effects of TPA on cell growth began within 1-2 h after the addition; and (c) cells completed S phase and arrested in G2. In addition, TPA induced a pronounced morphological change, which peaked by 1 h and gradually subsided over 24 h. In populations of cells synchronized in G1 using lovastatin, (a) addition of TPA blocked the onset of DNA synthesis up to the end of G1; (b) the lag between addition of the drug and onset of DNA synthesis was less than 30 min; and (c) addition of TPA at the end of G1 prevented the increased phosphorylation of p34cdc2, as determined by immunoprecipitation. The experiments reported here show that TPA transiently blocked the proliferation of Demel melanoma cells at the G1-S border and in G2, thus preventing cells from progressing through the cell cycle. These experiments suggest that pathways involving protein kinase C interact with and rapidly alter the molecular pathways involving p34cdc2 which regulate the onset of DNA synthesis and the G2-M transition.
Authors:
D L Coppock; J B Tansey; L Nathanson
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research     Volume:  3     ISSN:  1044-9523     ISO Abbreviation:  Cell Growth Differ.     Publication Date:  1992 Aug 
Date Detail:
Created Date:  1992-11-13     Completed Date:  1992-11-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9100024     Medline TA:  Cell Growth Differ     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  485-94     Citation Subset:  IM    
Affiliation:
Oncology Research Laboratory, Winthrop University Hospital, Mineola, New York 11501.
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MeSH Terms
Descriptor/Qualifier:
Breast Neoplasms / secondary
CDC2 Protein Kinase / metabolism*
Cell Division / drug effects
DNA Replication / drug effects
Depression, Chemical
Humans
Interphase / drug effects*
Male
Melanoma / secondary*
Middle Aged
Neoplasm Proteins / metabolism*
Phosphorylation / drug effects
Protein Kinase C / physiology
Protein Processing, Post-Translational / drug effects
Tetradecanoylphorbol Acetate / pharmacology*
Tumor Cells, Cultured / drug effects,  metabolism,  pathology
Chemical
Reg. No./Substance:
0/Neoplasm Proteins; 16561-29-8/Tetradecanoylphorbol Acetate; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.22/CDC2 Protein Kinase

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