Valaja T, Mahonen A, Pirskanen A, Mäenpää P H
Department of Biochemistry and Biotechnology, University of Kuopio, Finland.
Biochem Pharmacol. 1990 Oct 15;40(8):1827-32. doi: 10.1016/0006-2952(90)90363-p.
MC 903 is a new structural analog of the naturally occurring, biologically active 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. MC 903 and 1,25(OH)2D3 have shown similar receptor binding properties and comparable effects on leukemic cell differentiation. However, MC 903 is at least 100 times less potent in influencing calcium metabolism than 1,25(OH)2D3. We have therefore studied, how MC 903 competes for the binding sites of 1,25(OH)2D3, influences the 1,25(OH)2D3 induced synthesis of the most abundant bone non-collagenous protein, osteocalcin, and induces the activity of alkaline phosphatase in MG-63 human osteosarcoma cells. We found that the new compound binds to 1,25(OH)2D3 receptors and regulates receptor mRNA levels essentially like the natural ligand. Our results also indicate that MC 903 induces the synthesis of osteocalcin and the activity of alkaline phosphatase in MG-63 cells through a receptor-mediated process almost identically with 1,25(OH)2D3. Growth of the MG-63 cells was inhibited slightly more with MC 903 than with 1,25(OH)2D3.
MC 903是天然存在的具有生物活性的1,25 - 二羟基维生素D3 [1,25(OH)2D3]的一种新的结构类似物。MC 903和1,25(OH)2D3表现出相似的受体结合特性以及对白血病细胞分化的类似作用。然而，MC 903在影响钙代谢方面的效力比1,25(OH)2D3至少低100倍。因此，我们研究了MC 903如何竞争1,25(OH)2D3的结合位点，影响1,25(OH)2D3诱导的最丰富的骨非胶原蛋白骨钙素的合成，以及在MG - 63人骨肉瘤细胞中诱导碱性磷酸酶的活性。我们发现这种新化合物与1,25(OH)2D3受体结合，并基本上像天然配体一样调节受体mRNA水平。我们的结果还表明，MC 903通过受体介导的过程诱导MG - 63细胞中骨钙素的合成和碱性磷酸酶的活性，这几乎与1,25(OH)2D3相同。MC 903对MG - 63细胞生长的抑制作用比1,25(OH)2D3略强。
