Induction of myeloid differentiation of HL-60 cells with naphthalene sulfonamide calmodulin antagonists.
The naphthalene sulfonamide calmodulin antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide and N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide, both induce limited myeloid differentiation of the human promyelocytic cell line, HL-60. In addition, these inhibitors augment the differentiation observed when HL-60 cells are induced with retinoic acid, dimethyl sulfoxide, or dibutyryl cyclic adenosine monophosphate. The dose-response curve for HL-60 differentiation was consistent with the published 50% inhibitory dose for inhibition of calmodulin-activated phosphodiesterase and with the calmodulin drug-binding potential of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide and N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide and their less active congeners, N-(6-aminohexyl)-1-naphthalenesulfonamide and N-(4-aminobutyl)-2-naphthalenesulfonamide. These effects, of the naphthalene sulfonamide calmodulin antagonists, are consistent with a regulatory role for calmodulin in cell differentiation, but parallel effects on protein kinase C cannot be excluded.
D003994:Bucladesine / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D011493:Protein Kinase C / Q000032:analysis; D013449:Sulfonamides / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
D002147:Calmodulin; D013449:Sulfonamides; C040184:W 12; D014212:Tretinoin; D003994:Bucladesine; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; D011493:Protein Kinase C; D004121:Dimethyl Sulfoxide