EFFECTS OF CALMODULIN ANTAGONISTS AND CYTOCHALASINS ON PROLIFERATION AND DIFFERENTIATION OF HUMAN PROMYELOCYTIC LEUKEMIA-CELL LINE HL-60

Abstract

To identify the possible role of Ca2+-related proteins, calmodulin and microfilaments in leukemic cells, the effect of calmodulin antagonists and cytochalasins on proliferation and differentiaton of human promyelocytic leukemia HL-60 cells was examined. 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-aminohexyl)-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 differentiaton. 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.