Effects of calmodulin antagonists and cytochalasins on proliferation and differentiation of human promyelocytic leukemia cell line HL-60.
To identify the possible roles of Ca2+-related proteins, calmodulin and microfilaments in leukemic cells, we tested the effect of calmodulin antagonists and cytochalasins on proliferation and differentiation of human promyelocytic leukemic HL-60 cells. The growth of HL-60 was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide, and trifluoperazine dihydrochloride. In contrast, the 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-induced differentiation of HL-60, as judged by plasma-membrane antigenic changes detected by monoclonal antibodies (OKM1, OKT9), nitroblue tetrazolium reduction, and induction of phagocytotic capacity, was not inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide or N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide, although phagocytosis was depressed by N-(6-amino-hexyl)-5-chloro-1-naphthalenesulfonamide or N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide. Trifluoperazine dihydrochloride also failed to inhibit the antigenic change induced by 1,25-(OH)2D3. Cytochalasins B and D, microfilament-disrupting agents, inhibited the cytoplasmic division and the growth of HL-60 but did not inhibit the 1,25-(OH)2D3-induced differentiation. These findings suggest that the calmodulin- and microfilament-dependent process may be involved in the proliferation of HL-60, but not in the differentiation induced by 1,25-(OH)2D3.
D002117:Calcitriol / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003571:Cytochalasin B / Q000494:pharmacology*; D015638:Cytochalasin D; D003572:Cytochalasins / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010587:Phagocytosis / Q000187:drug effects; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology*
D002147:Calmodulin; D003572:Cytochalasins; D009363:Neoplasm Proteins; D013449:Sulfonamides; D015638:Cytochalasin D; D003571:Cytochalasin B; D002117:Calcitriol