EFFECTS OF A NOVEL VITAMIN-D ANALOG MC-903 ON CELL-PROLIFERATION AND DIFFERENTIATION INVITRO AND ON CALCIUM-METABOLISM INVIVO
EFFECTS OF A NOVEL VITAMIN-D ANALOG MC-903 ON CELL-PROLIFERATION AND DIFFERENTIATION INVITRO AND ON CALCIUM-METABOLISM INVIVO
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DOI：
10.1016/0006-2952(88)90177-3
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发表时间：
1988-03-01
影响因子：
5.8
通讯作者：
BRAMM, E
中科院分区：
文献类型：
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作者：
BINDERUP, L;BRAMM, E
MC 903是一种新型维生素D类似物，已使用人组织细胞淋巴瘤细胞系U937在体外测试了其对细胞分化和细胞增殖的影响，并在体内测试了其对大鼠钙代谢的影响。在本研究中，将MC 903与维生素D3的天然代谢物1 α，25-二羟基胆钙化醇[1，25（OH）2D3]及其合成类似物1 α-羟基胆钙化醇[1. α.（OH）D3]。发现MC 903是细胞分化的有效诱导剂，并且在与1，25（OH）2D3所观察到的浓度相当的浓度下抑制细胞增殖和DNA合成。1.alpha.（OH）D3仅在代谢转化为1，25（OH）2D3后才具有活性，其效力要低100倍以上。对大鼠口服或腹膜内给予MC 903表明，该化合物的活性比1，25（OH）2D3和1 α D3低至少100倍。（OH）D3引起高钙尿症、高钙血症和骨钙动员。MC 903的低维生素D活性通过将该化合物给予佝偻病大鼠进一步证实。MC 903对细胞增殖和细胞分化的强烈直接作用，加上其作为经典维生素D的活性降低，使该化合物成为研究人类增殖性疾病如银屑病的有趣候选物。
MC 903 is a novel vitamin D analogue which has been tested for its effects on cell differentiation and cell proliferation in vitro using the human histiocytic lymphoma cell line U937, and on calcium metabolism in rats in vivo. In the present investigation MC 903 was compared to the natural metabolite of vitamin D3, 1.alpha.,25-dihydroxycholecalciferol [1,25(OH)2D3] and to its synthetic analogue 1.alpha.-hydroxycholecalciferol [1.alpha.(OH)D3]. MC 903 was found to be a potent inducer of cell differentiation and to inhibit cell proliferation and DNA-synthesis in concentrations comparable to those observed with 1,25(OH)2D3. 1.alpha.(OH)D3, which is only active after metabolic conversion to 1,25(OH)2D3, was more than 100 times less potent. Oral or intraperitoneal administration of MC 903 to rats showed that the compound was at least 100 times less active than 1,25(OH)2D3 and 1.alpha.(OH)D3 in causing hypercalciuria, hypercalcemia and bone calcium mobilisation. The low vitamin D activity of MC 903 was further confirmed by administration of the compound to rachitic rats. The strong direct effects of MC 903 on cell proliferation and cell differentiation, coupled with its decreased activity as a classical vitamin D makes this compound an interesting candidate for studies in human proliferative disorders such as psoriasis.