Effects of a novel vitamin D analogue MC903 on cell proliferation and differentiation in vitro and on calcium metabolism in vivo.
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.
Binderup
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Department of Biology, Leo Pharmaceutical Products, Ballerup, Denmark.
Bramm
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D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism; D051381:Rats; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism; D012279:Rickets / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; C055085:calcipotriene; D002117:Calcitriol; D002118:Calcium