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 D3 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 D3, 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 D3. 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 D3. We observed distinct differences in sensitivity to the anti-proliferative activity of either 1,25-dihydroxyvitamin D3 or its analogues between cells of different origin.
Department of Tumor Immunology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław.
E
E
Marcinkowska
A
A
Kutner
C
C
Radzikowski
D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D015394:Molecular Structure; D027383:Papillomaviridae; D012867:Skin / Q000166:cytology; D013329:Structure-Activity Relationship; D014162:Transfection
D002117:Calcitriol