Effects of vitamin D-binding proteins on HL-60 cell differentiation induced by 26,26,26,27,27,27-hexafluoro-1α, 25-dihydroxyvitamin D 3

Abstract

Monocytic differentiation-inducing activity of 26,26,26,27,27,27-hexafluoro-1α,25-dihydroxyvitamin D 3 [26,27-F 6-1α,25-(OH) 2D 3] was re-evaluated in human promyelocytic leukemia (HL-60) cells in serum-supplemented or serum-free culture. The order of in vitro potency for reducing nitroblue tetrazolium (NBT) was 26,27-F 6-1 α,25-(OH) 2D 3 > 1 α,25-dihydroxyvitamin D 3 [1 α,25-(OH) 2D 3] = 26,26,26,27,27,27-F 6-1 α,23( S),25-trihydroxyvitamin D 3[26,27-F 6-1 α,23( S),25-(OH) 3D 3] under serum-supplemented culture conditions, whereas the order was 1 α, 25-(OH) 2D 3 = 26,27-F 6-1 α,25-(OH) 2D 3 > 26,27-F 6-1 α,23(S), 25-(OH) 3D 3 under serum-free culture conditions. This rank order for differentiation-inducing activity under serum-free culture conditions correlated well with the binding affinity of these analogs for vitamin D 3 receptor of HL-60 cells. The order of relative % binding affinity for the vitamin D-binding protein in fetal calf serum was 1 α,25-(OH) 2D 3 (100%)⪢26,27-F 6-1 α,25-(OH) 2D 3(5.1%) > 26,27-F 6-1 α,23( S),25-(OH) 3D 3 (<1%). These results suggest that serum vitamin D-binding proteins apparently modulate monocytic differentiation of HL-60 cells by 26,27-F 6- 1α,25-(OH) 2D 3 under serum-supplemented culture conditions.