Novel gemini vitamin D analogue: antitumoral effects on cancer cell lines and lack of calcemic activity in mice

Autores
Ferronato, María Julia; Salomón, Débora Gisele; Obiol, Diego Javier; Alonso, Eliana Noelia; Fall, Yagamare; Facchinetti, Maria Marta; Curino, Alejandro Carlos
Año de publicación
2014
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
1α,25-dihydroxyvitamin D3 (calcitriol) shows potent growth-inhibitory properties on different cancer cell lines although its hypercalcemic effects have severely hampered its therapeutic application. In collaboration with the laboratory of Organic Chemistry of the University of Vigo we synthesized a novel Gemini analogue of calcitriol, called UVB1, in order to maintain or increase the antitumor effects and decrease the calcemic activity. The aim of this study was to evaluate the antitumor action of UVB1 on different tumor cell lines, comparing its effects with those elicited by calcitriol, and studying its calcemic activity and its toxicity in mice. The analog exerts a significant decrease in cell count after treatment with UVB1 in HCT116 (human colorectal cancer), U251 (human glioblastoma), HN13 and HN12 (human head and neck squamous cell carcinoma) and T47D (human breast adenocarcinoma) cell lines. Also, UVB1 reduces cell migration of T98G (human glioblastoma multiforme), HN12 and LM3 (murine mammary adenocarcinoma) cell lines, while cell motility of HC11 (normal murine mammary epithelial cell line) is not affected. Since calcitriol has been shown to generate ROS which is involved in its antiproliferative activity, ROS production was determined in HN13 cell line after treatment with UVB1. An increase in the levels of ROS was observed. Cell cycle analysis by flow cytometry on the same cell line shows that UVB1 induces arrest in the G1/G0 phase and this result is accompanied by a decrease in cyclin D1 levels. The novel analogue, in contrast to calcitriol, did not cause hypercalcemic effects in BALB/c and nude mice. Additionally, histological examination of livers and kidneys showed no pathological changes. Furthermore, animals did not experiment changes in behavior, weight loss or haematocrit alterations. In conclusion, these results suggest that this Gemini analogue may have therapeutic potential as an antitumor drug.
Fil: Ferronato, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Salomón, Débora Gisele. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Obiol, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Alonso, Eliana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Fall, Yagamare. Universidad de Vigo; España
Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
III Reunión Internacional de Ciencias Farmacéuticas
Córdoba
Argentina
Society of Pharmaceutical Sciences and Research
Materia
ANALOGUE
ANTITUMOR-AGENTS
CALCITRIOL
CANCER
CELL-LINES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/238920
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/238920
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network_name_str CONICET Digital (CONICET)
spelling Novel gemini vitamin D analogue: antitumoral effects on cancer cell lines and lack of calcemic activity in miceFerronato, María JuliaSalomón, Débora GiseleObiol, Diego JavierAlonso, Eliana NoeliaFall, YagamareFacchinetti, Maria MartaCurino, Alejandro CarlosANALOGUEANTITUMOR-AGENTSCALCITRIOLCANCERCELL-LINEShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/31α,25-dihydroxyvitamin D3 (calcitriol) shows potent growth-inhibitory properties on different cancer cell lines although its hypercalcemic effects have severely hampered its therapeutic application. In collaboration with the laboratory of Organic Chemistry of the University of Vigo we synthesized a novel Gemini analogue of calcitriol, called UVB1, in order to maintain or increase the antitumor effects and decrease the calcemic activity. The aim of this study was to evaluate the antitumor action of UVB1 on different tumor cell lines, comparing its effects with those elicited by calcitriol, and studying its calcemic activity and its toxicity in mice. The analog exerts a significant decrease in cell count after treatment with UVB1 in HCT116 (human colorectal cancer), U251 (human glioblastoma), HN13 and HN12 (human head and neck squamous cell carcinoma) and T47D (human breast adenocarcinoma) cell lines. Also, UVB1 reduces cell migration of T98G (human glioblastoma multiforme), HN12 and LM3 (murine mammary adenocarcinoma) cell lines, while cell motility of HC11 (normal murine mammary epithelial cell line) is not affected. Since calcitriol has been shown to generate ROS which is involved in its antiproliferative activity, ROS production was determined in HN13 cell line after treatment with UVB1. An increase in the levels of ROS was observed. Cell cycle analysis by flow cytometry on the same cell line shows that UVB1 induces arrest in the G1/G0 phase and this result is accompanied by a decrease in cyclin D1 levels. The novel analogue, in contrast to calcitriol, did not cause hypercalcemic effects in BALB/c and nude mice. Additionally, histological examination of livers and kidneys showed no pathological changes. Furthermore, animals did not experiment changes in behavior, weight loss or haematocrit alterations. In conclusion, these results suggest that this Gemini analogue may have therapeutic potential as an antitumor drug.Fil: Ferronato, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Salomón, Débora Gisele. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Obiol, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Alonso, Eliana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Fall, Yagamare. Universidad de Vigo; EspañaFil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaIII Reunión Internacional de Ciencias FarmacéuticasCórdobaArgentinaSociety of Pharmaceutical Sciences and ResearchSociety of Pharmaceutical Sciences and Research2014info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/238920Novel gemini vitamin D analogue: antitumoral effects on cancer cell lines and lack of calcemic activity in mice; III Reunión Internacional de Ciencias Farmacéuticas; Córdoba; Argentina; 2014; 175-1762320-51480975-8232CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://ijpsr.com/wp-content/uploads/2015/05/Proceedings-RICIFa2014-Cordoba-ARGENTINA.pdfInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:03:22Zoai:ri.conicet.gov.ar:11336/238920instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:03:23.242CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Novel gemini vitamin D analogue: antitumoral effects on cancer cell lines and lack of calcemic activity in mice
title Novel gemini vitamin D analogue: antitumoral effects on cancer cell lines and lack of calcemic activity in mice
spellingShingle Novel gemini vitamin D analogue: antitumoral effects on cancer cell lines and lack of calcemic activity in mice
Ferronato, María Julia
ANALOGUE
ANTITUMOR-AGENTS
CALCITRIOL
CANCER
CELL-LINES
title_short Novel gemini vitamin D analogue: antitumoral effects on cancer cell lines and lack of calcemic activity in mice
title_full Novel gemini vitamin D analogue: antitumoral effects on cancer cell lines and lack of calcemic activity in mice
title_fullStr Novel gemini vitamin D analogue: antitumoral effects on cancer cell lines and lack of calcemic activity in mice
title_full_unstemmed Novel gemini vitamin D analogue: antitumoral effects on cancer cell lines and lack of calcemic activity in mice
title_sort Novel gemini vitamin D analogue: antitumoral effects on cancer cell lines and lack of calcemic activity in mice
dc.creator.none.fl_str_mv Ferronato, María Julia
Salomón, Débora Gisele
Obiol, Diego Javier
Alonso, Eliana Noelia
Fall, Yagamare
Facchinetti, Maria Marta
Curino, Alejandro Carlos
author Ferronato, María Julia
author_facet Ferronato, María Julia
Salomón, Débora Gisele
Obiol, Diego Javier
Alonso, Eliana Noelia
Fall, Yagamare
Facchinetti, Maria Marta
Curino, Alejandro Carlos
author_role author
author2 Salomón, Débora Gisele
Obiol, Diego Javier
Alonso, Eliana Noelia
Fall, Yagamare
Facchinetti, Maria Marta
Curino, Alejandro Carlos
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ANALOGUE
ANTITUMOR-AGENTS
CALCITRIOL
CANCER
CELL-LINES
topic ANALOGUE
ANTITUMOR-AGENTS
CALCITRIOL
CANCER
CELL-LINES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 1α,25-dihydroxyvitamin D3 (calcitriol) shows potent growth-inhibitory properties on different cancer cell lines although its hypercalcemic effects have severely hampered its therapeutic application. In collaboration with the laboratory of Organic Chemistry of the University of Vigo we synthesized a novel Gemini analogue of calcitriol, called UVB1, in order to maintain or increase the antitumor effects and decrease the calcemic activity. The aim of this study was to evaluate the antitumor action of UVB1 on different tumor cell lines, comparing its effects with those elicited by calcitriol, and studying its calcemic activity and its toxicity in mice. The analog exerts a significant decrease in cell count after treatment with UVB1 in HCT116 (human colorectal cancer), U251 (human glioblastoma), HN13 and HN12 (human head and neck squamous cell carcinoma) and T47D (human breast adenocarcinoma) cell lines. Also, UVB1 reduces cell migration of T98G (human glioblastoma multiforme), HN12 and LM3 (murine mammary adenocarcinoma) cell lines, while cell motility of HC11 (normal murine mammary epithelial cell line) is not affected. Since calcitriol has been shown to generate ROS which is involved in its antiproliferative activity, ROS production was determined in HN13 cell line after treatment with UVB1. An increase in the levels of ROS was observed. Cell cycle analysis by flow cytometry on the same cell line shows that UVB1 induces arrest in the G1/G0 phase and this result is accompanied by a decrease in cyclin D1 levels. The novel analogue, in contrast to calcitriol, did not cause hypercalcemic effects in BALB/c and nude mice. Additionally, histological examination of livers and kidneys showed no pathological changes. Furthermore, animals did not experiment changes in behavior, weight loss or haematocrit alterations. In conclusion, these results suggest that this Gemini analogue may have therapeutic potential as an antitumor drug.
Fil: Ferronato, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Salomón, Débora Gisele. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Obiol, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Alonso, Eliana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Fall, Yagamare. Universidad de Vigo; España
Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
III Reunión Internacional de Ciencias Farmacéuticas
Córdoba
Argentina
Society of Pharmaceutical Sciences and Research
description 1α,25-dihydroxyvitamin D3 (calcitriol) shows potent growth-inhibitory properties on different cancer cell lines although its hypercalcemic effects have severely hampered its therapeutic application. In collaboration with the laboratory of Organic Chemistry of the University of Vigo we synthesized a novel Gemini analogue of calcitriol, called UVB1, in order to maintain or increase the antitumor effects and decrease the calcemic activity. The aim of this study was to evaluate the antitumor action of UVB1 on different tumor cell lines, comparing its effects with those elicited by calcitriol, and studying its calcemic activity and its toxicity in mice. The analog exerts a significant decrease in cell count after treatment with UVB1 in HCT116 (human colorectal cancer), U251 (human glioblastoma), HN13 and HN12 (human head and neck squamous cell carcinoma) and T47D (human breast adenocarcinoma) cell lines. Also, UVB1 reduces cell migration of T98G (human glioblastoma multiforme), HN12 and LM3 (murine mammary adenocarcinoma) cell lines, while cell motility of HC11 (normal murine mammary epithelial cell line) is not affected. Since calcitriol has been shown to generate ROS which is involved in its antiproliferative activity, ROS production was determined in HN13 cell line after treatment with UVB1. An increase in the levels of ROS was observed. Cell cycle analysis by flow cytometry on the same cell line shows that UVB1 induces arrest in the G1/G0 phase and this result is accompanied by a decrease in cyclin D1 levels. The novel analogue, in contrast to calcitriol, did not cause hypercalcemic effects in BALB/c and nude mice. Additionally, histological examination of livers and kidneys showed no pathological changes. Furthermore, animals did not experiment changes in behavior, weight loss or haematocrit alterations. In conclusion, these results suggest that this Gemini analogue may have therapeutic potential as an antitumor drug.
publishDate 2014
dc.date.none.fl_str_mv 2014
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/238920
Novel gemini vitamin D analogue: antitumoral effects on cancer cell lines and lack of calcemic activity in mice; III Reunión Internacional de Ciencias Farmacéuticas; Córdoba; Argentina; 2014; 175-176
2320-5148
0975-8232
CONICET Digital
CONICET
url http://hdl.handle.net/11336/238920
identifier_str_mv Novel gemini vitamin D analogue: antitumoral effects on cancer cell lines and lack of calcemic activity in mice; III Reunión Internacional de Ciencias Farmacéuticas; Córdoba; Argentina; 2014; 175-176
2320-5148
0975-8232
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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eu_rights_str_mv openAccess
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dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Society of Pharmaceutical Sciences and Research
publisher.none.fl_str_mv Society of Pharmaceutical Sciences and Research
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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