Add time:08/01/2019         Source:sciencedirect.com

Novel vitamin D3 derivatives, 26 − homo − Δ22 − 1α25(S)-dihydroxyvitamin D3 and 26-homo-Δ22-1α25(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-Δ22-1α25(S)-(OH)2D3 was the greatest followed by 26-homo-Δ22-1α 25(R)-(OH)2D3. The ability to reduce NET was parallel to that to inhibit cellular proliferation. 26-Homo-Δ22-1α25(S)-(OH)2D3, 26-homo-Δ22-1α25(R)-(OH)2D3, 24-homo-24-F2-1α25-(OH)2D3, and 1α 24(R)-(OH)2-26-Cl-D3 were more active than 1α25-(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-Δ22-1α25(S)-(OH)2D3 plus interferon-γ (IFN-γ) but 14% in the treatment with 1α25-(OH)2D3 plus IFN-γ. 26-Homo-Δ22-1α 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-Δ22-1α 25(S)-(OH)2D3 and 26-homo-Δ22-1α25(R)-(OH)2D3, have preferential activity in inducting phenotypic differentiation and in inducing cell proliferation related c-myc mRNA activity.

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