title: Biological activities of 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3 on human promyelocytic leukemic HL-60 cells: effects of fetal bovine serum and of incubation time.
abstract: The hexafluorinated vitamin D3 analog, 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3[F6-1,25-(OH)2D3] is more potent than 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] regarding various physiological effects. When the biological potencies of vitamin D3 analogs were assessed 24 h after the addition by the induction of 24-hydroxylation activity in the human promyelocytic leukemia cell line, HL-60,F6-1,25-(OH)2D3 was 6 times as potent as 1,25-(OH)2D3 in a medium containing 5% fetal bovine serum. When the cells were cultured in a serum-free medium, F6-1,25-(OH)2D3 was only equipotent to 1,25-(OH)2D3. Considering a previous report demonstrating a weaker binding of F6-1,25-(OH)2D3 to serum vitamin D-binding protein (DBP) than 1,25-(OH)2D3, it seems that the resultant greater free fraction of F6-1,25-(OH)2D3 might account for its greater activity in a serum-containing medium. As assessed by the suppression of cell proliferation and the induction of cell differentiation along the monocyte/macrophage pathway which requires as long as 96 h for their assessment, the potency ratio of F6-1,25-(OH)2D3 to 1,25-(OH)2D3 increased as the levels of fetal bovine serum increased. It was of great interest that F6-1,25-(OH)2D3 was still significantly more potent than 1,25-(OH)2D3 even in a serum-free medium. Together with the data indicating the equipotency of F6-1,25-(OH)2D3 and 1,25-(OH)2D3 in the induction of 24-hydroxylation activity, it was suggested that decreased metabolic inactivation might contribute in part to the higher potency of F6-1,25-(OH)2D3 in the long-term effect.
authors.affiliation: Second Department of Internal Medicine, Osaka City University Medical School, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Okuno
authors.forename: M
authors.initials: M
authors.lastname: Inaba
authors.forename: Y
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: H
authors.initials: H
authors.lastname: Morii
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D005312:Fetal Blood / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D005466:Fluorocarbons
chemical_list: D002117:Calcitriol; D003470:Culture Media; C040488:26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3; D005466:Fluorocarbons