Document Detail


Effect of staurosporine on MOLT-4 cell progression through G2 and on cytokinesis.
MedLine Citation:
PMID:  8126077     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Staurosporine (SSP) is an inhibitor of a variety of protein kinases with an especially high affinity towards protein kinase C. Whereas SSP has been shown to halt the cell cycle progression of various normal, nontransformed cell types in G1, most virus transformed or tumor cells are unaffected in G1 but arrest in G2 phase. SSP has also been observed to increase the appearance of cells with higher DNA content, suggestive of endoreduplication, in cultures of tumor cells. Using multivariate flow cytometry (DNA content vs. expression of cyclin B, nuclear p120 protein, or protein reactive with Ki-67 antibody) which makes it possible to discriminate cells with identical DNA content but at different phases of the cycle, we have studied the cell cycle progression of human lymphocytic leukemic MOLT-4 cells in the presence of 0.1 microM SSP. MOLT-4 cells did not arrest in G1 or G2 phase in the presence of the inhibitor. Rather, they failed to undergo cytokinesis, entering G1 phase at higher DNA ploidy (tetraploidy; G1T), and then progressed through ST (rereplication) into G2T and MT. The rates of entrance to G2 and G2T were essentially identical, indicating that the rates of cell progression through S and ST as well as through G2 and G2T, respectively, were similar. Cells entrance to mitosis and mitotic chromatin condensation were also similar at the diploid and tetraploid DNA content level and were unaffected by 0.1 microM SSP. No evidence of growth imbalance (altered protein or RNA to DNA ratio) was observed in the case of tetraploid cells. The data show that, in the case of MOLT-4 cells, all events associated with the chromosome or DNA cycle were unaffected by SSP; the only target of the inhibitor appears to be kinase(s) controlling cytokinesis.
Authors:
F Traganos; J Gong; B Ardelt; Z Darzynkiewicz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  158     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  1994 Mar 
Date Detail:
Created Date:  1994-04-11     Completed Date:  1994-04-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  535-44     Citation Subset:  IM    
Affiliation:
Cancer Research Institute, New York Medical College, Elmsford 10523.
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MeSH Terms
Descriptor/Qualifier:
Alkaloids / pharmacology*
Cell Cycle / drug effects,  physiology*
Cell Division
Cell Separation / methods
Cyclins / analysis,  metabolism
DNA, Neoplasm / analysis,  genetics
Flow Cytometry
G1 Phase
G2 Phase*
Humans
Ki-67 Antigen
Leukemia, Lymphoid / genetics,  metabolism,  pathology*
Mitosis
Neoplasm Proteins / immunology
Nuclear Proteins / analysis,  immunology,  metabolism
Ploidies
RNA, Neoplasm / analysis,  genetics
S Phase
Staurosporine
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
R01 CA28704/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Alkaloids; 0/Cyclins; 0/DNA, Neoplasm; 0/Ki-67 Antigen; 0/NOL1 protein, human; 0/Neoplasm Proteins; 0/Nuclear Proteins; 0/RNA, Neoplasm; 62996-74-1/Staurosporine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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