CELL DIFFERENTIATING AND ANTIPROLIFERATIVE ACTIVITY OF SIDE-CHAIN MODIFIED ANALOGS OF 1,25-DIHYDROXYVITAMIN D-3

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 c ell line as a model. We also analyzed the influence of these compounds on the proliferation of HL60 cells, normal human keratinocytes, norma l fibroblasts from human skin and human keratinocytes transfected with human papillomavirus type 16. Two of the four analogues, i.e. those w ith extended side-chain, were found to display similar cell differenti ating 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 sens itivity to the anti-proliferative activity of either 1,25-dihydroxyvit amin D-3 or its analogues between cells of different origin. (C) 1998 Elsevier Science Ltd. All rights reserved.