title: Biological evaluation of new vitamin D2analogues.
abstract: 1,25-dihydroxyvitamin D3(1,25D), a steroid hormone which regulates calcium/phosphate homeostasis, has a broad spectrum of anti-cancer activities, including differentiation of acute myeloid leukemia (AML) cells. In order to avoid undesirable side effects such as hypercalcemia, low-calcemic analogues should be produced for therapeutic purposes. In this paper, we describe biological activities of double-point modified analogues of vitamin D2and we compare them to 1,25D and to paricalcitol, the drug used to treat secondary hyperparathyroidism. In vivo, our new analogues have lower calcemic effects, and lower toxicity in comparison to 1,25D. They have enhanced pro-differentiating and transcription-inducing activities in AML cells. Interestingly, differentiation effects do not correlate with the affinities of the analogues to the vitamin D receptor (VDR).
authors.affiliation: Faculty of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383 Wrocław, Poland.
authors.forename: Aoife
authors.initials: A
authors.lastname: Corcoran
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, Praza do Obradoiro, Santiago de Compostela 15782, A Coruña, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Bermudez
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, Praza do Obradoiro, Santiago de Compostela 15782, A Coruña, Spain.
authors.forename: Samuel
authors.initials: S
authors.lastname: Seoane
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, Praza do Obradoiro, Santiago de Compostela 15782, A Coruña, Spain.
authors.forename: Roman
authors.initials: R
authors.lastname: Perez-Fernandez
authors.affiliation: Pharmaceutical Research Institute, 8 Rydygiera, 01-793 Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krupa
authors.affiliation: Pharmaceutical Research Institute, 8 Rydygiera, 01-793 Warsaw, Poland.
authors.forename: Anita
authors.initials: A
authors.lastname: Pietraszek
authors.affiliation: Pharmaceutical Research Institute, 8 Rydygiera, 01-793 Warsaw, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Chodyński
authors.affiliation: Pharmaceutical Research Institute, 8 Rydygiera, 01-793 Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kutner
authors.affiliation: School of Immunity and Infection, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, West Midlands B15 2TT, UK.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Brown
authors.affiliation: Faculty of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383 Wrocław, Poland. Electronic address: ema@cs.uni.wroc.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Marcinkowska
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002454:Cell Differentiation; D004353:Drug Evaluation, Preclinical; D004872:Ergocalciferols / Q000138:chemical synthesis* / Q000737:chemistry* / Q000235:genetics; D018922:HL-60 Cells; D006706:Homeostasis; D006801:Humans; D006934:Hypercalcemia / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D051379:Mice; D017354:Point Mutation; D018167:Receptors, Calcitriol / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation; D065668:Vitamin D3 24-Hydroxylase / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D004872:Ergocalciferols; D018950:Lipopolysaccharide Receptors; D018167:Receptors, Calcitriol; C003564:1,25-dihydroxyergocalciferol; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase
keywords: Calcemic effects; Differentiation; Keratinocytes; Leukemia; vitamin D analogues; vitamin D receptor