| 12-O-tetradecanoylphorbol-13-acetate induces transient cell cycle arrest in G1 and G2 in metastatic melanoma cells: inhibition of phosphorylation of p34cdc2. | |
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MedLine Citation:
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PMID: 1390335 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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D L Coppock; J B Tansey; L Nathanson |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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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:
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Created Date: 1992-11-13 Completed Date: 1992-11-13 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9100024 Medline TA: Cell Growth Differ Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 485-94 Citation Subset: IM |
Affiliation:
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Oncology Research Laboratory, Winthrop University Hospital, Mineola, New York 11501. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Breast Neoplasms
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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:
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0/Neoplasm Proteins; 16561-29-8/Tetradecanoylphorbol Acetate; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.22/CDC2 Protein Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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