Combined calcitriol and menadione reduces experimental murine triple negative breast tumor

Autores
Bohl, Luciana Paola; Guizzardi, Solange Natali; Rodriguez, Valeria Andrea; Hinrichsen, Lucila Isabel; Rozados, Viviana Rosa; Cremonezzi, David César; Tolosa, Nori Graciela; Picotto, Gabriela
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background Calcitriol (D) or 1,25(OH)2D3 inhibits the growth of several tumor cells including breast cancer cells, by activating cell death pathways. Menadione (MEN), a glutathione-depleting compound, may be used to potentiate the antiproliferative actions of D on cancer cells. We have previously shown in vitro that MEN improved D-induced growth arrest on breast cancer cell lines, inducing oxidative stress and DNA damage via ROS generation. Treatment with MEN + D resulted more effective than D or MEN alone. Objective: To study the in vivo effect of calcitriol, MEN or their combination on the development of murine transplantable triple negative breast tumor M-406 in its syngeneic host. Methods Tumor M-406 was inoculated s.c., and when tumors reached the desired size, animals were randomly assigned to one of four groups receiving daily i.p. injections of either sterile saline solution (controls, C), MEN, D, or both (MEN + D). Body weight and tumor volume were recorded three times a week. Serum calcium was determined before and at the end of the treatment, at which time tumor samples were obtained for histological examination. Results None of the drugs, alone or in combination, affected mice body weight in the period studied. The combined treatment reduced tumor growth rate (C vs. MEN + D, P < 0.05) and the corresponding histological sections exhibited small remaining areas of viable tumor only in the periphery. A concomitant DNA fragmentation was observed in all treated groups and MEN potentiated the calcitriol effect on tumor growth. Conclusions As previously observed in vitro, treatment with MEN and D delayed tumor growth in vivo more efficiently than the individual drugs, with evident signals of apoptosis induction. Our results propose an alternative protocol to treat triple negative breast cancer, using GSH depleting drugs together with calcitriol, which would allow lower doses of the steroid to maintain the antitumor effect while diminishing its adverse pharmacological effects.
Fil: Bohl, Luciana Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Transferencia de Villa María. Universidad Nacional de Villa María. Centro de Investigaciones y Transferencia de Villa María; Argentina
Fil: Guizzardi, Solange Natali. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Rodriguez, Valeria Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina
Fil: Hinrichsen, Lucila Isabel. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Rozados, Viviana Rosa. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Cremonezzi, David César. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina
Fil: Tolosa, Nori Graciela. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Picotto, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina
Materia
Calcitriol
Cell Death
In Vivo Tumor Growth
Menadione
Triple Negative Breast Cancer
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/64151
Acceder
id CONICETDig_c070f4a0fea50fb3a605ffccde592191
oai_identifier_str oai:ri.conicet.gov.ar:11336/64151
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Combined calcitriol and menadione reduces experimental murine triple negative breast tumorBohl, Luciana PaolaGuizzardi, Solange NataliRodriguez, Valeria AndreaHinrichsen, Lucila IsabelRozados, Viviana RosaCremonezzi, David CésarTolosa, Nori GracielaPicotto, GabrielaCalcitriolCell DeathIn Vivo Tumor GrowthMenadioneTriple Negative Breast Cancerhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background Calcitriol (D) or 1,25(OH)2D3 inhibits the growth of several tumor cells including breast cancer cells, by activating cell death pathways. Menadione (MEN), a glutathione-depleting compound, may be used to potentiate the antiproliferative actions of D on cancer cells. We have previously shown in vitro that MEN improved D-induced growth arrest on breast cancer cell lines, inducing oxidative stress and DNA damage via ROS generation. Treatment with MEN + D resulted more effective than D or MEN alone. Objective: To study the in vivo effect of calcitriol, MEN or their combination on the development of murine transplantable triple negative breast tumor M-406 in its syngeneic host. Methods Tumor M-406 was inoculated s.c., and when tumors reached the desired size, animals were randomly assigned to one of four groups receiving daily i.p. injections of either sterile saline solution (controls, C), MEN, D, or both (MEN + D). Body weight and tumor volume were recorded three times a week. Serum calcium was determined before and at the end of the treatment, at which time tumor samples were obtained for histological examination. Results None of the drugs, alone or in combination, affected mice body weight in the period studied. The combined treatment reduced tumor growth rate (C vs. MEN + D, P < 0.05) and the corresponding histological sections exhibited small remaining areas of viable tumor only in the periphery. A concomitant DNA fragmentation was observed in all treated groups and MEN potentiated the calcitriol effect on tumor growth. Conclusions As previously observed in vitro, treatment with MEN and D delayed tumor growth in vivo more efficiently than the individual drugs, with evident signals of apoptosis induction. Our results propose an alternative protocol to treat triple negative breast cancer, using GSH depleting drugs together with calcitriol, which would allow lower doses of the steroid to maintain the antitumor effect while diminishing its adverse pharmacological effects.Fil: Bohl, Luciana Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Transferencia de Villa María. Universidad Nacional de Villa María. Centro de Investigaciones y Transferencia de Villa María; ArgentinaFil: Guizzardi, Solange Natali. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Rodriguez, Valeria Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Hinrichsen, Lucila Isabel. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Rozados, Viviana Rosa. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Cremonezzi, David César. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Tolosa, Nori Graciela. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Picotto, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaElsevier France-editions Scientifiques Medicales Elsevier2017-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/64151Bohl, Luciana Paola; Guizzardi, Solange Natali; Rodriguez, Valeria Andrea; Hinrichsen, Lucila Isabel; Rozados, Viviana Rosa; et al.; Combined calcitriol and menadione reduces experimental murine triple negative breast tumor; Elsevier France-editions Scientifiques Medicales Elsevier; Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie; 94; 10-2017; 21-260753-33221950-6007CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0753332217323880info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biopha.2017.07.058info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:53:57Zoai:ri.conicet.gov.ar:11336/64151instacron: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:34982025-09-03 09:53:58.366CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Combined calcitriol and menadione reduces experimental murine triple negative breast tumor
title Combined calcitriol and menadione reduces experimental murine triple negative breast tumor
spellingShingle Combined calcitriol and menadione reduces experimental murine triple negative breast tumor
Bohl, Luciana Paola
Calcitriol
Cell Death
In Vivo Tumor Growth
Menadione
Triple Negative Breast Cancer
title_short Combined calcitriol and menadione reduces experimental murine triple negative breast tumor
title_full Combined calcitriol and menadione reduces experimental murine triple negative breast tumor
title_fullStr Combined calcitriol and menadione reduces experimental murine triple negative breast tumor
title_full_unstemmed Combined calcitriol and menadione reduces experimental murine triple negative breast tumor
title_sort Combined calcitriol and menadione reduces experimental murine triple negative breast tumor
dc.creator.none.fl_str_mv Bohl, Luciana Paola
Guizzardi, Solange Natali
Rodriguez, Valeria Andrea
Hinrichsen, Lucila Isabel
Rozados, Viviana Rosa
Cremonezzi, David César
Tolosa, Nori Graciela
Picotto, Gabriela
author Bohl, Luciana Paola
author_facet Bohl, Luciana Paola
Guizzardi, Solange Natali
Rodriguez, Valeria Andrea
Hinrichsen, Lucila Isabel
Rozados, Viviana Rosa
Cremonezzi, David César
Tolosa, Nori Graciela
Picotto, Gabriela
author_role author
author2 Guizzardi, Solange Natali
Rodriguez, Valeria Andrea
Hinrichsen, Lucila Isabel
Rozados, Viviana Rosa
Cremonezzi, David César
Tolosa, Nori Graciela
Picotto, Gabriela
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Calcitriol
Cell Death
In Vivo Tumor Growth
Menadione
Triple Negative Breast Cancer
topic Calcitriol
Cell Death
In Vivo Tumor Growth
Menadione
Triple Negative Breast Cancer
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background Calcitriol (D) or 1,25(OH)2D3 inhibits the growth of several tumor cells including breast cancer cells, by activating cell death pathways. Menadione (MEN), a glutathione-depleting compound, may be used to potentiate the antiproliferative actions of D on cancer cells. We have previously shown in vitro that MEN improved D-induced growth arrest on breast cancer cell lines, inducing oxidative stress and DNA damage via ROS generation. Treatment with MEN + D resulted more effective than D or MEN alone. Objective: To study the in vivo effect of calcitriol, MEN or their combination on the development of murine transplantable triple negative breast tumor M-406 in its syngeneic host. Methods Tumor M-406 was inoculated s.c., and when tumors reached the desired size, animals were randomly assigned to one of four groups receiving daily i.p. injections of either sterile saline solution (controls, C), MEN, D, or both (MEN + D). Body weight and tumor volume were recorded three times a week. Serum calcium was determined before and at the end of the treatment, at which time tumor samples were obtained for histological examination. Results None of the drugs, alone or in combination, affected mice body weight in the period studied. The combined treatment reduced tumor growth rate (C vs. MEN + D, P < 0.05) and the corresponding histological sections exhibited small remaining areas of viable tumor only in the periphery. A concomitant DNA fragmentation was observed in all treated groups and MEN potentiated the calcitriol effect on tumor growth. Conclusions As previously observed in vitro, treatment with MEN and D delayed tumor growth in vivo more efficiently than the individual drugs, with evident signals of apoptosis induction. Our results propose an alternative protocol to treat triple negative breast cancer, using GSH depleting drugs together with calcitriol, which would allow lower doses of the steroid to maintain the antitumor effect while diminishing its adverse pharmacological effects.
Fil: Bohl, Luciana Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Transferencia de Villa María. Universidad Nacional de Villa María. Centro de Investigaciones y Transferencia de Villa María; Argentina
Fil: Guizzardi, Solange Natali. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Rodriguez, Valeria Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina
Fil: Hinrichsen, Lucila Isabel. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Rozados, Viviana Rosa. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Cremonezzi, David César. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina
Fil: Tolosa, Nori Graciela. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Picotto, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina
description Background Calcitriol (D) or 1,25(OH)2D3 inhibits the growth of several tumor cells including breast cancer cells, by activating cell death pathways. Menadione (MEN), a glutathione-depleting compound, may be used to potentiate the antiproliferative actions of D on cancer cells. We have previously shown in vitro that MEN improved D-induced growth arrest on breast cancer cell lines, inducing oxidative stress and DNA damage via ROS generation. Treatment with MEN + D resulted more effective than D or MEN alone. Objective: To study the in vivo effect of calcitriol, MEN or their combination on the development of murine transplantable triple negative breast tumor M-406 in its syngeneic host. Methods Tumor M-406 was inoculated s.c., and when tumors reached the desired size, animals were randomly assigned to one of four groups receiving daily i.p. injections of either sterile saline solution (controls, C), MEN, D, or both (MEN + D). Body weight and tumor volume were recorded three times a week. Serum calcium was determined before and at the end of the treatment, at which time tumor samples were obtained for histological examination. Results None of the drugs, alone or in combination, affected mice body weight in the period studied. The combined treatment reduced tumor growth rate (C vs. MEN + D, P < 0.05) and the corresponding histological sections exhibited small remaining areas of viable tumor only in the periphery. A concomitant DNA fragmentation was observed in all treated groups and MEN potentiated the calcitriol effect on tumor growth. Conclusions As previously observed in vitro, treatment with MEN and D delayed tumor growth in vivo more efficiently than the individual drugs, with evident signals of apoptosis induction. Our results propose an alternative protocol to treat triple negative breast cancer, using GSH depleting drugs together with calcitriol, which would allow lower doses of the steroid to maintain the antitumor effect while diminishing its adverse pharmacological effects.
publishDate 2017
dc.date.none.fl_str_mv 2017-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/64151
Bohl, Luciana Paola; Guizzardi, Solange Natali; Rodriguez, Valeria Andrea; Hinrichsen, Lucila Isabel; Rozados, Viviana Rosa; et al.; Combined calcitriol and menadione reduces experimental murine triple negative breast tumor; Elsevier France-editions Scientifiques Medicales Elsevier; Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie; 94; 10-2017; 21-26
0753-3322
1950-6007
CONICET Digital
CONICET
url http://hdl.handle.net/11336/64151
identifier_str_mv Bohl, Luciana Paola; Guizzardi, Solange Natali; Rodriguez, Valeria Andrea; Hinrichsen, Lucila Isabel; Rozados, Viviana Rosa; et al.; Combined calcitriol and menadione reduces experimental murine triple negative breast tumor; Elsevier France-editions Scientifiques Medicales Elsevier; Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie; 94; 10-2017; 21-26
0753-3322
1950-6007
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0753332217323880
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biopha.2017.07.058
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Elsevier France-editions Scientifiques Medicales Elsevier
publisher.none.fl_str_mv Elsevier France-editions Scientifiques Medicales Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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