Synergistic induction of erythroid differentiation of mouse erythroleukemia (MEL) cells by inhibitors of topoisomerases and protein tyrosine kinases.
In vitro erythroid differentiation of mouse erythroleukemia (MEL) cells was induced by combinations of topoisomerase and protein kinase inhibitors. Neither inhibitor alone exhibited inducing activity. Although inhibitors of topoisomerases I and II were equally effective in the synergistic induction of erythroid differentiation, only inhibitors of tyrosine kinases, not of serine/threonine kinases, exhibited synergistic activity. The erythroid differentiation induced by the combination of topoisomerase and protein tyrosine kinase inhibitors was distinguished from that induced by typical erythroid inducing agents such as DMSO or HMBA by (1) earlier hemoglobin accumulation in the cells and (2) insensitivity to specific inhibitors (dexamethasone and sodium orthovanadate) of MEL cell differentiation.
Watanabe
T
T
Institute of Applied Microbiology, University of Tokyo, Japan.
Kume
T
T
Tsuneizumi
K
K
Kondo
K
K
Shiraishi
T
T
Oishi
M
M
D000081:Acetamides / Q000494:pharmacology; D000677:Amsacrine / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002166:Camptothecin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002934:Cinnamates / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013440:Sulfides / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014638:Vanadates / Q000494:pharmacology
D000081:Acetamides; D002934:Cinnamates; D006454:Hemoglobins; D013440:Sulfides; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; C060747:ST 638; D014638:Vanadates; D016685:Mitomycin; C067472:methyl 2,5-dihydroxycinnamate; D011505:Protein-Tyrosine Kinases; C014026:hexamethylene bisacetamide; D002166:Camptothecin; D004121:Dimethyl Sulfoxide