Effect of staurosporine on MOLT-4 cell progression through G2 and on cytokinesis
Autor: | Barbara Ardelt, Zbigniew Darzynkiewicz, Jianping Gong, Frank Traganos |
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Rok vydání: | 1994 |
Předmět: |
G2 Phase
Cell division Physiology Clinical Biochemistry Cell Cyclin B Mitosis Cell Separation S Phase Alkaloids Cyclins Tumor Cells Cultured medicine Humans Endoreduplication RNA Neoplasm tRNA Methyltransferases Ploidies biology Cell Cycle fungi G1 Phase Nuclear Proteins food and beverages DNA Neoplasm Cell Biology Cell cycle Flow Cytometry Staurosporine Leukemia Lymphoid Neoplasm Proteins Cell biology Ki-67 Antigen medicine.anatomical_structure Cell culture biology.protein Cell Division Cytokinesis |
Zdroj: | Journal of Cellular Physiology. 158:535-544 |
ISSN: | 1097-4652 0021-9541 |
Popis: | 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. |
Databáze: | OpenAIRE |
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