Marcinkowska E, Kutner A, Radzikowski C
Department of Tumor Immunology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław.
J Steroid Biochem Mol Biol. 1998 Oct;67(1):71-8. doi: 10.1016/s0960-0760(98)00065-x.
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.
除了在体内具有钙动员活性外，1,25 - 二羟基维生素D3还具有在体外诱导人早幼粒细胞白血病细胞分化的能力。我们以HL60细胞系为模型，研究了1,25 - 二羟基维生素D3的四种新型类似物的细胞分化活性。我们还分析了这些化合物对HL60细胞、正常人角质形成细胞、人皮肤正常成纤维细胞以及转染了16型人乳头瘤病毒的人角质形成细胞增殖的影响。四种类似物中的两种，即具有延长侧链的那些，被发现具有与1,25 - 二羟基维生素D3相似的细胞分化和抗增殖活性。另外两种类似物，其侧链缩短并包含一个额外的羟基，显示出比1,25 - 二羟基维生素D3低得多的活性。我们观察到不同来源的细胞对1,25 - 二羟基维生素D3或其类似物的抗增殖活性的敏感性存在明显差异。
