Tyrosine kinase inhibitor-induced differentiation of K-562 cells: alterations of cell cycle and cell surface phenotype.
Protein tyrosine kinase (PTK) inhibitor herbimycin A inhibited proliferation, induced accumulation of cells in the G0/G1 phase of the cell cycle and a marked increae of hemoglobin-producing human leukemic K-562 cells in vitro. The isoflavonoid PTK- and topoisomerase II inhibitor genistein produced a similar effect with the accumulation of cells in the G2/M phase of cell cycle. Genistein potentiated the effect of herbimycin A on the cell cycle (i.e. decreased the proportion of S-phase cells) and induced an increased proportion of hemoglobin-producing cells. Genistein, but not herbimycin A induced a marked increase in cell surface expression of CD15 (LewisX) antigen. Both of these agents down-regulated CD45 (leukocyte common antigen) and monocyte-associated CD14 antigen on K-562 cells. Neither genistein nor herbimycin A induced increased cell surface expression of glycophorin.
Cancer Research Institute, Slovak Academy of Sciences, Bratislava.
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L
Hunáková
J
J
Sedlák
M
M
Klobusická
J
J
Duraj
B
B
Chorváth
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D016227:Benzoquinones; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D019833:Genistein; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D047029:Lactams, Macrocyclic; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D051379:Mice; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D016227:Benzoquinones; D006454:Hemoglobins; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases