The natural tyrosine kinase inhibitor genistein produces cell cycle arrest and apoptosis in Jurkat T-leukemia cells
Autor: | Fausto Grignani, Ildo Nicoletti, Graziella Migliorati, Carlo Riccardi, R. Moraca, M. Cristina Pagliacci, Fabrizio Spinozzi |
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Rok vydání: | 1994 |
Předmět: |
Cancer Research
Leukemia T-Cell Time Factors medicine.drug_class T cell Genistein Antineoplastic Agents Apoptosis Biology Jurkat cells Tyrosine-kinase inhibitor Cell Line chemistry.chemical_compound Tumor Cells Cultured medicine Humans Dose-Response Relationship Drug Cell growth Cell Cycle food and beverages DNA Neoplasm Hematology Protein-Tyrosine Kinases cell cycle genistein Isoflavones Kinetics medicine.anatomical_structure Oncology chemistry Cancer research Phosphorylation Growth inhibition Tyrosine kinase Cell Division |
Zdroj: | Leukemia Research. 18:431-439 |
ISSN: | 0145-2126 |
DOI: | 10.1016/0145-2126(94)90079-5 |
Popis: | Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinases. We analyzed the effects of genistein on in vitro growth, cell-cycle progression and chromatin structure of Jurkat cells, a T-cell leukemia line with a constitutively increased tyrosine phosphorylation pattern. Exposure of in vitro cultured Jurkat cells to genistein resulted in a dose-dependent, growth inhibition. Cell-cycle analysis of genistein-treated cells revealed a G2/M arrest at low genistein concentrations (5-10 micrograms/ml), while at higher doses (20-30 micrograms/ml) there was also a perturbation in S-phase progression. The derangements in cell-cycle control were followed by apoptotic death of genistein-treated cells. Immunocytochemical analysis of cells stained with a FITC-conjugated anti-phosphotyrosine monoclonal antibody showed that 30 micrograms/ml genistein effectively inhibit tyrosine kinase activity in cultured Jurkat cells. Our results indicate that the natural isoflavone genistein antagonizes tumor cell growth through both cell-cycle arrest and induction of apoptosis and suggest that it could be a promising new agent in cancer therapy. |
Databáze: | OpenAIRE |
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