Effects of CalmodulinAntagonistsand Cytochalasinson Proliferationand Differentiationof HumanPromyelocyticLeukemiaCell Line HL-601

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 A/-(6-aminohexyl)-5-chloro-1 naphthalenesulfonamide, A/-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide, and trifluoperazine dihydrochloride. In contrast, the 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-induced differentia tion 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 A/-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide or A/-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide, although phagocytosis was depressed by A/-(6-aminohexyl)-5-chloro-1 -naphthalenesulfonamide or A/-(4-aminobutyl)-5chloro-2-naphthalenesulfonamide. Trifluoperazine dihydrochlo ride 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 HL60 but did not inhibit the 1¿S-fOHfeDs-induced differentiation. These findings suggest that the calmodulinand microfilamentdependent process may be involved in the proliferation of HL60, but not in the differentiation induced by 1¿S-iOHfeDa.