title: Vitamin D analogue: potent antiproliferative effects on cancer cell lines and lack of hypercalcemic activity.
abstract: The active form of vitamin D3, 1α,25(OH)2D3, plays a major role in maintaining calcium/phosphate homeostasis. In addition, it is a potent antiproliferative and pro-differentiating agent. Unfortunately, it usually causes hypercalcemia in vivo when effective antitumour doses are used. It has therefore been found necessary to synthesise new analogues that retain or even increase the antitumour effects but preclude hypercalcemia. This report presents the synthesis of a novel Gemini vitamin D analogue (UVB1) and its biological evaluation. We demonstrate that this compound has potent antitumoural effects over a wide panel of tumour cell lines while showing lack of hypercalcemic activity and toxicity effects in in vivo assays.
authors: Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca (INIBIBB-CONICET), Centro Científico Tecnológico Bahía Blanca, Bahía Blanca, Argentina.
authors: María Julia
authors: MJ
authors: Ferronato
authors: Débora Gisele
authors: DG
authors: Salomón
authors: María Eugenia
authors: ME
authors: Fermento
authors: Norberto Ariel
authors: NA
authors: Gandini
authors: Alejandro
authors: A
authors: López Romero
authors: Marcos Lois
authors: ML
authors: Rivadulla
authors: Xenxo
authors: X
authors: Pérez-García
authors: Generosa
authors: G
authors: Gómez
authors: Manuel
authors: M
authors: Pérez
authors: Yagamare
authors: Y
authors: Fall
authors: María Marta
authors: MM
authors: Facchinetti
authors: Alejandro Carlos
authors: AC
authors: Curino
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D002118:Calcium / Q000097:blood; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000139:chemically induced*; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D013997:Time Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; C000604793:UVB1 compound; D014807:Vitamin D; D002118:Calcium
keywords: Antiproliferative agents; Antitumour activity; Cancer treatment; Cell line; Gemini