Effects of novel 26,27-dialkyl analogs of 1α,25-dihydroxyvitamin D3 on differentiation-inducing activity of human promyelocytic leukemia (HL-60) cells in serum-supplemented or serum-free culture

Add time:08/23/2019    Source:sciencedirect.com

Monocylic differentiation-inducing activity of steroidal side chain-lengthened 26,27-dialkyl analogs of 1α,25-dihydroxyvitamin D3 was examined in human promyelocytic leukemia (HL-60) cells in serumsupplemented or serum-free culture. The order of in vitro potency for reducing nitroblue tetrazolium was 1α,25-dihydroxy-26,27-dimethylvilamin D3, ≧ 1α,25-dihydroxyvitamin D3 > 1α,25-dihydroxy-26,27-diethylvitamin D3 ⪢ 1 α,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.

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