Cell differentiating and anti-proliferative activity of side-chain modified analogues of 1,25-dihydroxyvitamin D3

Besides its calcium mobilizing activity in vivo, 1,25-dihydroxyvitamin D(3) has the ability to induce differentiation of human promyelocytic leukemia cells in vitro. We studied the cell differentiating activity of four novel analogues of 1,25-dihydroxyvitamin D(3), using the HL60 cell line as a model. We also analyzed the influence of these compounds on the proliferation of HL60 cells, normal human keratinocytes, normal fibroblasts from human skin and human keratinocytes transfected with human papillomavirus type 16. Two of the four analogues, i.e. those with extended side-chain, were found to display similar cell differentiating and anti-proliferative activities as 1,25-dihydroxyvitamin D(3). The other two analogues, with a shortened side-chain which included an additional hydroxyl, showed a substantially lower activity than that of 1,25-dihydroxyvitamin D(3). We observed distinct differences in sensitivity to the anti-proliferative activity of either 1,25-dihydroxyvitamin D(3) or its analogues between cells of different origin. (C) 1998 Elsevier Science Ltd. All rights reserved.