Effects of novel 26,27-dialkyl analogs of 1 alpha,25-dihydroxyvitamin D3 on differentiation-inducing activity of human promyelocytic leukemia (HL-60) cells in serum-supplemented or serum-free culture.
Monocytic differentiation-inducing activity of steroidal side chain-lengthened 26,27-dialkyl analogs of 1 alpha,25-dihydroxyvitamin D3 was examined in human promyelocytic leukemia (HL-60) cells in serum-supplemented or serum-free culture. The order of in vitro potency for reducing nitroblue tetrazolium was 1 alpha,25-dihydroxy-26,27-dimethylvitamin D3 greater than or equal to 1 alpha,25-dihydroxy-26,27-diethylvitamin D3 much greater than 1 alpha,25-dihydroxy-26,27-dipropylvitamin D3 under serum-free culture conditions. Analysis by sucrose density-gradient centrifugation or polyethylene glycol precipitation technique showed that the potency order for differentiation-inducing activity correlated well with binding affinity of these analogs for vitamin D3 receptor of HL-60 cells. Under serum-supplemented culture conditions, the lack of correlation between biologic activity and analog-binding affinity for receptor was caused by differences in binding affinity of these analogs for serum vitamin D-binding proteins. These results suggest that serum vitamin D-binding proteins apparently modulate monocytic differentiation of HL-60 cells by these analogs under serum-supplemented culture conditions.
Honda
A
A
Department of Biochemistry, Tokyo College of Pharmacy, Japan.
Mori
Y
Y
Otomo
S
S
Ishizuka
S
S
Ikekawa
N
N
D002117:Calcitriol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology*; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014809:Vitamin D-Binding Protein / Q000378:metabolism
C055037:26,27-diethyl-1,25-dihydroxyvitamin D3; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D014809:Vitamin D-Binding Protein; C069098:1,25-dihydroxy-26,27-dipropylcholecalciferol; D009580:Nitroblue Tetrazolium; C046127:1,25-dihydroxy-26,27-dimethylcholecalciferol; D002117:Calcitriol