Biological activity of vitamin D3 derivatives in inducing differentiation of HL-60 human promyelocytic leukemia cells.
Induction of cell differentiation by twenty-one derivatives of vitamin D3 and their binding affinity for the receptor of 1 alpha,25-dihydroxyvitamin D3, an active vitamin D3 metabolite, were examined using HL-60 human promyelocytic leukemia cells and chick intestinal cytosol, respectively. 1 alpha,24(R)-dihydroxy-26-chlorovitamin D3 is found to be more active than 1 alpha,24(R)-dihydroxyvitamin D3 and 1 alpha,25-dihydroxyvitamin D3 in the two abilities to induce the differentiation and to bind to the receptor. The results suggest that a hydroxy group at C-1 position of vitamin D3 and a hydroxy or oxo group at C-25 or C-24 position are essential for both abilities. In diastereoisomers of 1 alpha,25-dihydroxyvitamin D3-26,23-lactone, synthesized (23 S,25 S) 1 alpha,25-dihydroxyvitamin D3-26,23-lactone was more active in both abilities than the natural metabolite, (23 S,25 R) 1 alpha,25-dihydroxyvitamin D3-26,23-lactone, which shows anti-vitamin D action.
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002645:Chickens; D002762:Cholecalciferol / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D009580:Nitroblue Tetrazolium; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism; D013237:Stereoisomerism; D014808:Vitamin D Deficiency / Q000378:metabolism
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002762:Cholecalciferol; D009580:Nitroblue Tetrazolium