新型维生素D3衍生物，26-高-δ22-脱氢-1α,25(S)-二羟基维生素D3和26-高-δ22-脱氢-1α,25(R)-二羟基维生素D3：在c-myc mRNA产生及诱导HL-60细胞表型分化中的优先活性

Novel vitamin D3 derivatives, 26-homo-delta 22-dehydro-1 alpha,25(S)-dihydroxyvitamin D3 and 26-homo-delta 22-dehydro-1 alpha,25(R)-dihydroxyvitamin D3: preferential activity in c-myc mRNA production and in induction of phenotypic differentiation of HL-60 cells.

作者信息

Koizumi T, Nakao Y, Ishizuka S, Oshida J, Hara N, Ikekawa N, Fijita T

机构信息

Department of Medicine, Kobe University School of Medicine, Japan.

出版信息

Arch Biochem Biophys. 1990 Feb 1;276(2):310-6. doi: 10.1016/0003-9861(90)90725-e.

DOI:10.1016/0003-9861(90)90725-e

PMID:2407190

Abstract

Novel vitamin D3 derivatives, 26-homo-delta 22-1 alpha,25(S)-dihydroxyvitamin D3 and 26-homo-delta 22-1 alpha,25(R)-dihydroxyvitamin D3 were compared with the native hormone, 1,25-dihydroxyvitamin D3, and with other vitamin D3 derivatives, in inhibition of cell growth, induction of phenotypic differentiation, and c-myc mRNA reduction of HL-60 cells. The degree of inhibition in cell growth caused by 26-homo-delta 22-1 alpha,25(S)-(OH)2D3 was the greatest followed by 26-homo-delta 22-1 alpha,25(R)-(OH)2D3. The ability to reduce NBT was parallel to that to inhibit cellular proliferation. 26-homo-delta 22-1 alpha,25(S)-(OH)2D3, 26-homo-delta 22-1 alpha,25(R)-(OH)2D3, 24-homo-24-F2-1 alpha,25-(OH)2D3, and 1 alpha,24(R)-(OH)2-26-Cl-D3 were more active than 1 alpha,25-(OH)2D3 in the induction of OK-M1+ and OK-Mo-2+ HL-60 cells. Using two color flow cytometric analysis, the percentages of OK-M5(+)- and OK-DR(+)-HL-60 cells were 33% in the treatment with 26-homo-delta 22-1 alpha,25(S)-(OH)2D3 plus interferon-gamma (IFN-gamma) but 14% in the treatment with 1 alpha,25-(OH)2D3 plus IFN-gamma. 26-Homo-delta 22-1 alpha,25(S)-(OH)2D3 has an inhibitory effect on c-myc reduction in treated HL-60 cells. These results suggest that the novel vitamin D3 derivatives, 26-homo-delta 22-1 alpha,25(S)-(OH)2D3 and 26-homo-delta 22-1 alpha,25(R)-(OH)2D3, have preferential activity in inducing phenotypic differentiation and in inducing cell proliferation related c-myc mRNA activity.

摘要

将新型维生素D3衍生物26-高-δ22-1α,25(S)-二羟基维生素D3和26-高-δ22-1α,25(R)-二羟基维生素D3与天然激素1,25-二羟基维生素D3以及其他维生素D3衍生物在抑制HL-60细胞生长、诱导表型分化和降低c-myc mRNA水平方面进行了比较。26-高-δ22-1α,25(S)-(OH)2D3引起的细胞生长抑制程度最大，其次是26-高-δ22-1α,25(R)-(OH)2D3。还原NBT的能力与抑制细胞增殖的能力平行。26-高-δ22-1α,25(S)-(OH)2D3、26-高-δ22-1α,25(R)-(OH)2D3、24-高-24-F2-1α,25-(OH)2D3和1α,24(R)-(OH)2-26-Cl-D3在诱导OK-M1+和OK-Mo-2+ HL-60细胞方面比1α,25-(OH)2D3更具活性。使用双色流式细胞术分析，在26-高-δ22-1α,25(S)-(OH)2D3加干扰素-γ（IFN-γ）处理中，OK-M5(+)和OK-DR(+) HL-60细胞的百分比为33%，而在1α,25-(OH)2D3加IFN-γ处理中为14%。26-高-δ22-1α,25(S)-(OH)2D3对处理后的HL-60细胞中c-myc的降低有抑制作用。这些结果表明，新型维生素D3衍生物26-高-δ22-1α,25(S)-(OH)2D3和26-高-δ22-1α,25(R)-(OH)2D3在诱导表型分化和诱导与细胞增殖相关的c-myc mRNA活性方面具有优先活性。