Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells

Autores
Liaudat, Ana Cecilia; Bohl, Luciana Paola; Tolosa, Nori Graciela; Maletto, Belkys Angélica; Pistoresi, Maria Cristina; Picotto, Gabriela
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The prognosis and incidence of colon cancer are linked to vitamin D3 serum levels. To evaluate the effects of D,L-buthionine-S,R-sulfoximine (BSO), 1,25(OH)2D3 and their combination on intestinal Caco-2 cell growth, to elucidate the possible cellular mechanisms involved in their antiproliferative action, and to determine whether BSO acts as a sensitizer to 1,25(OH)2D3 treatment, enabling minimization of the toxic effects caused by high doses of the steroid. Human colon cancer Caco-2 cells were treated with 1,25(OH)2D3, BSO, both, or vehicle. Cell proliferation was evaluated by crystal violet staining. Cell cycle and mitochondrial membrane potential were measured by flow cytometry. Total glutathione, catalase, superoxide dismutase, superoxide anion levels, and alkaline phosphatase activities were analyzed by spectrophotometry. DNA fragmentation was evaluated using the terminal dUTP nick end labeling assay. BSO and 1,25(OH)2D3 inhibited Caco-2 cell growth, an effect that was higher with the combined treatment. The antiproliferative effect produced by the combination could be protected by ascorbic acid. BSO plus 1,25(OH)2D3 induced cell cycle arrest and suppressed cell division. Total glutathione decreased and superoxide anion increased with BSO and BSO plus 1,25(OH)2D3. Catalase activity increased with the combined treatment. Mitochondrial membrane potential and alkaline phosphatase activity were altered by 1,25(OH)2D3 alone or plus BSO. The percentage of terminal dUTP nick end labeling-positive cells was increased. BSO increases the antiproliferative effect of 1,25(OH)2D3 on Caco-2 cells through induction of oxidative stress, which occurs simultaneously with DNA breakage. The antioxidant system can partially compensate the damage induced by BSO plus 1,25(OH)2D3. Cell differentiation induction is also involved in the response to the combined treatment.
Fil: Liaudat, Ana Cecilia. 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: Bohl, Luciana Paola. 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: Tolosa, Nori Graciela. 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: Maletto, Belkys Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Pistoresi, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; 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
Materia
1,25(Oh)2d3
Buthionine Sulfoximine
Caco-2 Cells
Oxidative Stress
Cell Cycle
Celldifferentiation
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:11336/31962
Acceder
id CONICETDig_c68d315f436c96cbfb276460317d71f6
oai_identifier_str oai:ri.conicet.gov.ar:11336/31962
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cellsLiaudat, Ana CeciliaBohl, Luciana PaolaTolosa, Nori GracielaMaletto, Belkys AngélicaPistoresi, Maria CristinaPicotto, Gabriela1,25(Oh)2d3Buthionine SulfoximineCaco-2 CellsOxidative StressCell CycleCelldifferentiationhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3The prognosis and incidence of colon cancer are linked to vitamin D3 serum levels. To evaluate the effects of D,L-buthionine-S,R-sulfoximine (BSO), 1,25(OH)2D3 and their combination on intestinal Caco-2 cell growth, to elucidate the possible cellular mechanisms involved in their antiproliferative action, and to determine whether BSO acts as a sensitizer to 1,25(OH)2D3 treatment, enabling minimization of the toxic effects caused by high doses of the steroid. Human colon cancer Caco-2 cells were treated with 1,25(OH)2D3, BSO, both, or vehicle. Cell proliferation was evaluated by crystal violet staining. Cell cycle and mitochondrial membrane potential were measured by flow cytometry. Total glutathione, catalase, superoxide dismutase, superoxide anion levels, and alkaline phosphatase activities were analyzed by spectrophotometry. DNA fragmentation was evaluated using the terminal dUTP nick end labeling assay. BSO and 1,25(OH)2D3 inhibited Caco-2 cell growth, an effect that was higher with the combined treatment. The antiproliferative effect produced by the combination could be protected by ascorbic acid. BSO plus 1,25(OH)2D3 induced cell cycle arrest and suppressed cell division. Total glutathione decreased and superoxide anion increased with BSO and BSO plus 1,25(OH)2D3. Catalase activity increased with the combined treatment. Mitochondrial membrane potential and alkaline phosphatase activity were altered by 1,25(OH)2D3 alone or plus BSO. The percentage of terminal dUTP nick end labeling-positive cells was increased. BSO increases the antiproliferative effect of 1,25(OH)2D3 on Caco-2 cells through induction of oxidative stress, which occurs simultaneously with DNA breakage. The antioxidant system can partially compensate the damage induced by BSO plus 1,25(OH)2D3. Cell differentiation induction is also involved in the response to the combined treatment.Fil: Liaudat, Ana Cecilia. 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: Bohl, Luciana Paola. 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: Tolosa, Nori Graciela. 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: Maletto, Belkys Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Pistoresi, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; 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; ArgentinaLippincott Williams2014-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/31962Picotto, Gabriela; Liaudat, Ana Cecilia; Pistoresi, Maria Cristina; Maletto, Belkys Angélica; Tolosa, Nori Graciela; Bohl, Luciana Paola; et al.; Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells; Lippincott Williams; Anticancer Drugs; 25; 7; 8-2014; 810-8180959-4973CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1097/CAD.0000000000000109info:eu-repo/semantics/altIdentifier/url/http://journals.lww.com/anti-cancerdrugs/pages/articleviewer.aspx?year=2014&issue=08000&article=00008&type=abstractinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:10:07Zoai:ri.conicet.gov.ar:11336/31962instacron: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:34982025-10-15 15:10:07.856CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells
title Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells
spellingShingle Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells
Liaudat, Ana Cecilia
1,25(Oh)2d3
Buthionine Sulfoximine
Caco-2 Cells
Oxidative Stress
Cell Cycle
Celldifferentiation
title_short Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells
title_full Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells
title_fullStr Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells
title_full_unstemmed Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells
title_sort Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells
dc.creator.none.fl_str_mv Liaudat, Ana Cecilia
Bohl, Luciana Paola
Tolosa, Nori Graciela
Maletto, Belkys Angélica
Pistoresi, Maria Cristina
Picotto, Gabriela
author Liaudat, Ana Cecilia
author_facet Liaudat, Ana Cecilia
Bohl, Luciana Paola
Tolosa, Nori Graciela
Maletto, Belkys Angélica
Pistoresi, Maria Cristina
Picotto, Gabriela
author_role author
author2 Bohl, Luciana Paola
Tolosa, Nori Graciela
Maletto, Belkys Angélica
Pistoresi, Maria Cristina
Picotto, Gabriela
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv 1,25(Oh)2d3
Buthionine Sulfoximine
Caco-2 Cells
Oxidative Stress
Cell Cycle
Celldifferentiation
topic 1,25(Oh)2d3
Buthionine Sulfoximine
Caco-2 Cells
Oxidative Stress
Cell Cycle
Celldifferentiation
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The prognosis and incidence of colon cancer are linked to vitamin D3 serum levels. To evaluate the effects of D,L-buthionine-S,R-sulfoximine (BSO), 1,25(OH)2D3 and their combination on intestinal Caco-2 cell growth, to elucidate the possible cellular mechanisms involved in their antiproliferative action, and to determine whether BSO acts as a sensitizer to 1,25(OH)2D3 treatment, enabling minimization of the toxic effects caused by high doses of the steroid. Human colon cancer Caco-2 cells were treated with 1,25(OH)2D3, BSO, both, or vehicle. Cell proliferation was evaluated by crystal violet staining. Cell cycle and mitochondrial membrane potential were measured by flow cytometry. Total glutathione, catalase, superoxide dismutase, superoxide anion levels, and alkaline phosphatase activities were analyzed by spectrophotometry. DNA fragmentation was evaluated using the terminal dUTP nick end labeling assay. BSO and 1,25(OH)2D3 inhibited Caco-2 cell growth, an effect that was higher with the combined treatment. The antiproliferative effect produced by the combination could be protected by ascorbic acid. BSO plus 1,25(OH)2D3 induced cell cycle arrest and suppressed cell division. Total glutathione decreased and superoxide anion increased with BSO and BSO plus 1,25(OH)2D3. Catalase activity increased with the combined treatment. Mitochondrial membrane potential and alkaline phosphatase activity were altered by 1,25(OH)2D3 alone or plus BSO. The percentage of terminal dUTP nick end labeling-positive cells was increased. BSO increases the antiproliferative effect of 1,25(OH)2D3 on Caco-2 cells through induction of oxidative stress, which occurs simultaneously with DNA breakage. The antioxidant system can partially compensate the damage induced by BSO plus 1,25(OH)2D3. Cell differentiation induction is also involved in the response to the combined treatment.
Fil: Liaudat, Ana Cecilia. 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: Bohl, Luciana Paola. 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: Tolosa, Nori Graciela. 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: Maletto, Belkys Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Pistoresi, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; 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
description The prognosis and incidence of colon cancer are linked to vitamin D3 serum levels. To evaluate the effects of D,L-buthionine-S,R-sulfoximine (BSO), 1,25(OH)2D3 and their combination on intestinal Caco-2 cell growth, to elucidate the possible cellular mechanisms involved in their antiproliferative action, and to determine whether BSO acts as a sensitizer to 1,25(OH)2D3 treatment, enabling minimization of the toxic effects caused by high doses of the steroid. Human colon cancer Caco-2 cells were treated with 1,25(OH)2D3, BSO, both, or vehicle. Cell proliferation was evaluated by crystal violet staining. Cell cycle and mitochondrial membrane potential were measured by flow cytometry. Total glutathione, catalase, superoxide dismutase, superoxide anion levels, and alkaline phosphatase activities were analyzed by spectrophotometry. DNA fragmentation was evaluated using the terminal dUTP nick end labeling assay. BSO and 1,25(OH)2D3 inhibited Caco-2 cell growth, an effect that was higher with the combined treatment. The antiproliferative effect produced by the combination could be protected by ascorbic acid. BSO plus 1,25(OH)2D3 induced cell cycle arrest and suppressed cell division. Total glutathione decreased and superoxide anion increased with BSO and BSO plus 1,25(OH)2D3. Catalase activity increased with the combined treatment. Mitochondrial membrane potential and alkaline phosphatase activity were altered by 1,25(OH)2D3 alone or plus BSO. The percentage of terminal dUTP nick end labeling-positive cells was increased. BSO increases the antiproliferative effect of 1,25(OH)2D3 on Caco-2 cells through induction of oxidative stress, which occurs simultaneously with DNA breakage. The antioxidant system can partially compensate the damage induced by BSO plus 1,25(OH)2D3. Cell differentiation induction is also involved in the response to the combined treatment.
publishDate 2014
dc.date.none.fl_str_mv 2014-08
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/11336/31962
Picotto, Gabriela; Liaudat, Ana Cecilia; Pistoresi, Maria Cristina; Maletto, Belkys Angélica; Tolosa, Nori Graciela; Bohl, Luciana Paola; et al.; Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells; Lippincott Williams; Anticancer Drugs; 25; 7; 8-2014; 810-818
0959-4973
CONICET Digital
CONICET
url http://hdl.handle.net/11336/31962
identifier_str_mv Picotto, Gabriela; Liaudat, Ana Cecilia; Pistoresi, Maria Cristina; Maletto, Belkys Angélica; Tolosa, Nori Graciela; Bohl, Luciana Paola; et al.; Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells; Lippincott Williams; Anticancer Drugs; 25; 7; 8-2014; 810-818
0959-4973
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1097/CAD.0000000000000109
info:eu-repo/semantics/altIdentifier/url/http://journals.lww.com/anti-cancerdrugs/pages/articleviewer.aspx?year=2014&issue=08000&article=00008&type=abstract
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
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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score 13.22299

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