Differential effect of protein kinase inhibitors (staurosporine and CGP 41,251) on TPA-induced homotypic aggregation and cell surface adhesion antigen expression in human monoblastoid cell line U-937.
The phorbolester (TPA)-induced homotypic aggregation of human monoblastoid U-937 cells was completely abolished by staurosporine, but not by a new selective protein kinase C inhibitor, benzoylated staurosporine derivative CGP 41,251, a compound with known anti-tumor and drug resistance modulating activity. Staurosporine, a protein kinase inhibitor with broad profile of inhibitory activity on diverse protein kinases, but not CGP 41,251 substantially inhibited the TPA-induced up-regulation of intercellular adhesion molecule-1 (ICAM-1, CD54) and to a lesser extent also its ligand CD11a. These results suggest that protein kinase C-independent mechanisms, inhibited by staurosporine but not by the selective PKC inhibitor CGP 41,251 are involved in the TPA-induced homotypic adhesion and modulation of cell surface adhesion antigens in the human monoblastoid cell line U-937.
Sedlák
J
J
Cancer Research Institute, Slovak Academy of Sciences, Bratislava.
Sulíková
M
M
Hunáková
L
L
Chorváth
B
B
D000470:Alkaloids / Q000494:pharmacology*; D002449:Cell Aggregation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects* / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology* / Q000473:pathology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019311:Staurosporine / Q000031:analogs & derivatives; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D018799:Intercellular Adhesion Molecule-1; D011493:Protein Kinase C; D019311:Staurosporine; C059539:midostaurin; D013755:Tetradecanoylphorbol Acetate