EFFECTS OF VITAMIN D-BINDING PROTEINS ON HL-60 CELL-DIFFERENTIATION INDUCED BY 26,26,26,27,27,27-HEXAFLUORO-1-ALPHA,25-DIHYDROXYVITAMIN-D3

Monocytic differentiation-inducing activity of 26,26,26,27,27,27-hexafluoro-1-alpha,25-dihydroxyvitamin D3 [26,27-F6-1-alpha,25-(OH)2D3] 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-F6-1-alpha,25-(OH)2D3 > 1-alpha,25-dihydroxyvitamin D3 [1-alpha,25-(OH)2D3] = 26,26,26,27,27,27-F6-1-alpha,23(S),25-trihydroxyvitamin D3 [26,27-F6-1-alpha,23(S),25-(OH)3D3] under serum-supplemented culture conditions, whereas the order was 1-alpha,25-(OH)2D3 = 26,27-F6-1-alpha,25-(OH)2D3 > 26,27-F6-1-alpha,23(S),25-(OH)3D3 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 D3 receptor of HL-60 cells. The order of relative % binding affinity for the vitamin D-binding protein in fetal calf serum was 1-alpha,25-(OH)2D3 (100%) >> 26,27-F6-1-alpha,25-(OH)2D3 (5.1%) > 26,27-F6-1-alpha,23(S),25-(OH)3D3 (< 1%). These results suggest that serum vitamin D-binding proteins apparently modulate monocytic differentiation of HL-60 cells by 26,27-F6-1-alpha,25-(OH)2D3 under serum-supplemented culture conditions.