title: The alkynylphosphonate analogue of calcitriol EM1 has potent anti-metastatic effects in breast cancer.
abstract: The active form of vitamin D3, calcitriol, plays a major role in maintaining calcium/phosphate homeostasis. In addition, it is a potent antiproliferative and prodifferentiating agent. However, when effective antitumor doses of calcitriol are employed, hypercalcemic effects are observed, thus precluding its therapeutic application. To overcome this problem, structural analogues have been designed with the aim at retaining or even increasing the antitumor effects while decreasing its calcemic activity. This report shows the biological evaluation of an alkynylphosphonate vitamin D less-calcemic analogue in a murine model of breast cancer. We demonstrate that this compound has potent anti-metastatic effects through its action over cellular migration and invasion likely mediated through the up-regulation of E-cadherin expression. Based on the current in vitro and in vivo results, EM1 is a promising candidate as a therapeutic agent in breast cancer.
authors.affiliation: Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca, Centro Científico Tecnológico Bahía Blanca (INIBIBB-CONICET), Bahía Blanca, Argentina.
authors.forename: María J
authors.initials: MJ
authors.lastname: Ferronato
authors.affiliation: Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca, Centro Científico Tecnológico Bahía Blanca (INIBIBB-CONICET), Bahía Blanca, Argentina.
authors.forename: Diego J
authors.initials: DJ
authors.lastname: Obiol
authors.affiliation: Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca, Centro Científico Tecnológico Bahía Blanca (INIBIBB-CONICET), Bahía Blanca, Argentina.
authors.forename: María E
authors.initials: ME
authors.lastname: Fermento
authors.affiliation: Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca, Centro Científico Tecnológico Bahía Blanca (INIBIBB-CONICET), Bahía Blanca, Argentina.
authors.forename: Norberto A
authors.initials: NA
authors.lastname: Gandini
authors.affiliation: Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca, Centro Científico Tecnológico Bahía Blanca (INIBIBB-CONICET), Bahía Blanca, Argentina.
authors.forename: Eliana N
authors.initials: EN
authors.lastname: Alonso
authors.affiliation: Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca, Centro Científico Tecnológico Bahía Blanca (INIBIBB-CONICET), Bahía Blanca, Argentina.
authors.forename: Débora G
authors.initials: DG
authors.lastname: Salomón
authors.affiliation: Laboratorio de Química Orgánica, Departamento de Química, Universidad Nacional del Sur (INQUISUR), Bahía Blanca, Argentina.
authors.forename: Cristian
authors.initials: C
authors.lastname: Vitale
authors.affiliation: Laboratorio de Química Orgánica, Departamento de Química, Universidad Nacional del Sur (INQUISUR), Bahía Blanca, Argentina.
authors.forename: Evangelina
authors.initials: E
authors.lastname: Mascaró
authors.affiliation: Departamento de Química Orgánica, Facultad de Química and Instituto de Investigación Biomedica (IBI), University of Vigo, Campus Lagoas de Marcosende, 36310 Vigo, Spain.
authors.forename: Yagamare
authors.initials: Y
authors.lastname: Fall
authors.affiliation: Area de Investigación, Instituto de Oncología "Angel H. Roffo", Buenos Aires, Argentina.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Raimondi
authors.affiliation: Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca, Centro Científico Tecnológico Bahía Blanca (INIBIBB-CONICET), Bahía Blanca, Argentina.
authors.forename: Alejandro C
authors.initials: AC
authors.lastname: Curino
authors.affiliation: Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca, Centro Científico Tecnológico Bahía Blanca (INIBIBB-CONICET), Bahía Blanca, Argentina. Electronic address: facchinm@criba.edu.ar.
authors.forename: María M
authors.initials: MM
authors.lastname: Facchinetti
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D063065:Organophosphonates / Q000494:pharmacology*
chemical_list: D063065:Organophosphonates; D002117:Calcitriol
keywords: Alkynylphosphonate; Analogue; Breast cancer; Calcitriol; Vitamin D