Polyamines in lα, 25-Dihydroxycholecalciferol-Induced Differentiation of Human Promyelocytic Leukemia Cells, HL-60

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Abstract
The human promyelocytic leukemia cell line, HL-60, differentiated into macrophage/mohocytes in the presence of lα,25-dihydroxycholecalciferol [lα,25(OH)2D3], as assessed by the percentage of morphologically mature cells and their ability to reduce nitroblue tetrazolium. In this study of the mechanism involved, the activities of orriithine decarboxylase and spermidine/spermihe-N1-acetyltransferase (SAT), the ratelimiting enzymes of polyamine metabolism, as well as the cellular levels of polyamine were measured. ODC activity reached a peak 24 h after the addition of lα,25(OH)2D3 and then decreased, while SAT activity gradually increased as differentiation commenced. An increase in putrescine and decreases in spermidine and spermine were also observed. Addition of α-difluoro-methylornithine, an irreversible inhibitor of ODC, with or without methylglyoxalbis(guanylhydrazone), an inhibitor of S-adenosylmethionihe decarboxylase, caused no effect on lα,25(OH)2D3-induced cell differentiation, although the cellular levels of putrescine and spermidine decreased markedly. Addition of adifluoromethylornithine markedly suppressed cell proliferation; this effect was reversed by the addition of exogenous putrescine. Addition of exogenous spermidine or spermine to overcome activation of SAT also had no effect on lα,25(OH)2D3-induced cell differentiation. These results suggest both that polyamine metabolism is not important in lα,25(OH)2D3-induced differentiation of HL-60 cells, but that it is intimately involved in proliferation of these cells. (Endocrinology118: 1849–1855, 1986)