Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells

Autores
Español, Alejandro Javier; Sanchez, Yamila; Salem, Agustina Reina; Obregon, Jaqueline; Sales, María Elena
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Triple negative breast cancer is more aggressive than other breast cancer subtypes and constitutes a public health problem worldwide since it has high morbidity and mortality due to the lack of defined therapeutic targets. Resistance to chemotherapy complicates the evolution of these patients. Several authors have highlighted the participation of nicotinic acetylcholine receptors (nAChR) in the modulation of conventional chemotherapy treatment in lung, head and neck, oral and nasal cavity, and pancreatic cancers. However, in smoking cancer patients, the action of nicotine on nAChR expressed in the breast or other organs near the tumor during chemotherapy treatment is less known.AIMTo investigate the effect of nicotine on paclitaxel treatment and the signaling pathways involved in human breast MDA-MB231 tumor cells.METHODSCells were treated with paclitaxel alone or in combination with nicotine, administered for one or three 48 h cycles. The effect of the addition of nicotine (in a concentration similar to that found in smokers? blood) on the treatment with paclitaxel (in a therapeutic concentration) was determined by using the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The signaling mediators involved in this effect were determined by using selective inhibitors. We also investigated nAChR expression, and ATP ?binding cassette? G2 drug transporter (ABCG2) expression and its modulation by the different treatments by Western blot. The effect of the treatments on apoptosis induction was determined by flow cytometry using annexin-V and 7AAD markers. RESULTSOur results confirmed that the treatment with paclitaxel reduced MDA-MB231 cell viability in a concentration-dependent manner and that the presence of nicotine reversed the cytotoxic effect induced by paclitaxel by involving the expression of functional α7 and α9 nAChRs in these cells. The action of nicotine on paclitaxel treatment was linked to the modulation of the protein kinase C, mitogen-activated protein kinase, extracellular signal-regulated kinase, and NF-B signaling pathways, and to an up-regulation of ABCG2 protein expression. We also detected that nicotine significantly reduced the increase in cell apoptosis induced by paclitaxel treatment. Moreover, we observed that the presence of nicotine reduced the efficacy of paclitaxel treatment administered in three cycles to MDA-MB231 tumor cells. CONCLUSIONOur findings point to nAChRs as responsible for the decrease in the chemotherapeutic effect of paclitaxel in triple negative tumors. Thus, they should be considered as targets in smoking patients.
Fil: Español, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Sanchez, Yamila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Salem, Agustina Reina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Obregon, Jaqueline. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Sales, María Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Materia
NICOTINIC
RECEPTORS
BREAST
CANCER
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:11336/215595

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spelling Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cellsEspañol, Alejandro JavierSanchez, YamilaSalem, Agustina ReinaObregon, JaquelineSales, María ElenaNICOTINICRECEPTORSBREASTCANCERhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Triple negative breast cancer is more aggressive than other breast cancer subtypes and constitutes a public health problem worldwide since it has high morbidity and mortality due to the lack of defined therapeutic targets. Resistance to chemotherapy complicates the evolution of these patients. Several authors have highlighted the participation of nicotinic acetylcholine receptors (nAChR) in the modulation of conventional chemotherapy treatment in lung, head and neck, oral and nasal cavity, and pancreatic cancers. However, in smoking cancer patients, the action of nicotine on nAChR expressed in the breast or other organs near the tumor during chemotherapy treatment is less known.AIMTo investigate the effect of nicotine on paclitaxel treatment and the signaling pathways involved in human breast MDA-MB231 tumor cells.METHODSCells were treated with paclitaxel alone or in combination with nicotine, administered for one or three 48 h cycles. The effect of the addition of nicotine (in a concentration similar to that found in smokers? blood) on the treatment with paclitaxel (in a therapeutic concentration) was determined by using the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The signaling mediators involved in this effect were determined by using selective inhibitors. We also investigated nAChR expression, and ATP ?binding cassette? G2 drug transporter (ABCG2) expression and its modulation by the different treatments by Western blot. The effect of the treatments on apoptosis induction was determined by flow cytometry using annexin-V and 7AAD markers. RESULTSOur results confirmed that the treatment with paclitaxel reduced MDA-MB231 cell viability in a concentration-dependent manner and that the presence of nicotine reversed the cytotoxic effect induced by paclitaxel by involving the expression of functional α7 and α9 nAChRs in these cells. The action of nicotine on paclitaxel treatment was linked to the modulation of the protein kinase C, mitogen-activated protein kinase, extracellular signal-regulated kinase, and NF-B signaling pathways, and to an up-regulation of ABCG2 protein expression. We also detected that nicotine significantly reduced the increase in cell apoptosis induced by paclitaxel treatment. Moreover, we observed that the presence of nicotine reduced the efficacy of paclitaxel treatment administered in three cycles to MDA-MB231 tumor cells. CONCLUSIONOur findings point to nAChRs as responsible for the decrease in the chemotherapeutic effect of paclitaxel in triple negative tumors. Thus, they should be considered as targets in smoking patients.Fil: Español, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Sanchez, Yamila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Salem, Agustina Reina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Obregon, Jaqueline. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Sales, María Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaBaishideng Publishing Group Inc.2022-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/215595Español, Alejandro Javier; Sanchez, Yamila; Salem, Agustina Reina; Obregon, Jaqueline; Sales, María Elena; Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells; Baishideng Publishing Group Inc.; World Journal of Clinical Oncology; 13; 6; 4-2022; 505-5192218-4333CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.5306/wjco.v13.i6.505info:eu-repo/semantics/altIdentifier/url/https://www.wjgnet.com/2218-4333/full/v13/i6/505.htminfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:34:06Zoai:ri.conicet.gov.ar:11336/215595instacron: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 09:34:06.673CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells
title Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells
spellingShingle Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells
Español, Alejandro Javier
NICOTINIC
RECEPTORS
BREAST
CANCER
title_short Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells
title_full Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells
title_fullStr Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells
title_full_unstemmed Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells
title_sort Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells
dc.creator.none.fl_str_mv Español, Alejandro Javier
Sanchez, Yamila
Salem, Agustina Reina
Obregon, Jaqueline
Sales, María Elena
author Español, Alejandro Javier
author_facet Español, Alejandro Javier
Sanchez, Yamila
Salem, Agustina Reina
Obregon, Jaqueline
Sales, María Elena
author_role author
author2 Sanchez, Yamila
Salem, Agustina Reina
Obregon, Jaqueline
Sales, María Elena
author2_role author
author
author
author
dc.subject.none.fl_str_mv NICOTINIC
RECEPTORS
BREAST
CANCER
topic NICOTINIC
RECEPTORS
BREAST
CANCER
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Triple negative breast cancer is more aggressive than other breast cancer subtypes and constitutes a public health problem worldwide since it has high morbidity and mortality due to the lack of defined therapeutic targets. Resistance to chemotherapy complicates the evolution of these patients. Several authors have highlighted the participation of nicotinic acetylcholine receptors (nAChR) in the modulation of conventional chemotherapy treatment in lung, head and neck, oral and nasal cavity, and pancreatic cancers. However, in smoking cancer patients, the action of nicotine on nAChR expressed in the breast or other organs near the tumor during chemotherapy treatment is less known.AIMTo investigate the effect of nicotine on paclitaxel treatment and the signaling pathways involved in human breast MDA-MB231 tumor cells.METHODSCells were treated with paclitaxel alone or in combination with nicotine, administered for one or three 48 h cycles. The effect of the addition of nicotine (in a concentration similar to that found in smokers? blood) on the treatment with paclitaxel (in a therapeutic concentration) was determined by using the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The signaling mediators involved in this effect were determined by using selective inhibitors. We also investigated nAChR expression, and ATP ?binding cassette? G2 drug transporter (ABCG2) expression and its modulation by the different treatments by Western blot. The effect of the treatments on apoptosis induction was determined by flow cytometry using annexin-V and 7AAD markers. RESULTSOur results confirmed that the treatment with paclitaxel reduced MDA-MB231 cell viability in a concentration-dependent manner and that the presence of nicotine reversed the cytotoxic effect induced by paclitaxel by involving the expression of functional α7 and α9 nAChRs in these cells. The action of nicotine on paclitaxel treatment was linked to the modulation of the protein kinase C, mitogen-activated protein kinase, extracellular signal-regulated kinase, and NF-B signaling pathways, and to an up-regulation of ABCG2 protein expression. We also detected that nicotine significantly reduced the increase in cell apoptosis induced by paclitaxel treatment. Moreover, we observed that the presence of nicotine reduced the efficacy of paclitaxel treatment administered in three cycles to MDA-MB231 tumor cells. CONCLUSIONOur findings point to nAChRs as responsible for the decrease in the chemotherapeutic effect of paclitaxel in triple negative tumors. Thus, they should be considered as targets in smoking patients.
Fil: Español, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Sanchez, Yamila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Salem, Agustina Reina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Obregon, Jaqueline. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Sales, María Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
description Triple negative breast cancer is more aggressive than other breast cancer subtypes and constitutes a public health problem worldwide since it has high morbidity and mortality due to the lack of defined therapeutic targets. Resistance to chemotherapy complicates the evolution of these patients. Several authors have highlighted the participation of nicotinic acetylcholine receptors (nAChR) in the modulation of conventional chemotherapy treatment in lung, head and neck, oral and nasal cavity, and pancreatic cancers. However, in smoking cancer patients, the action of nicotine on nAChR expressed in the breast or other organs near the tumor during chemotherapy treatment is less known.AIMTo investigate the effect of nicotine on paclitaxel treatment and the signaling pathways involved in human breast MDA-MB231 tumor cells.METHODSCells were treated with paclitaxel alone or in combination with nicotine, administered for one or three 48 h cycles. The effect of the addition of nicotine (in a concentration similar to that found in smokers? blood) on the treatment with paclitaxel (in a therapeutic concentration) was determined by using the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The signaling mediators involved in this effect were determined by using selective inhibitors. We also investigated nAChR expression, and ATP ?binding cassette? G2 drug transporter (ABCG2) expression and its modulation by the different treatments by Western blot. The effect of the treatments on apoptosis induction was determined by flow cytometry using annexin-V and 7AAD markers. RESULTSOur results confirmed that the treatment with paclitaxel reduced MDA-MB231 cell viability in a concentration-dependent manner and that the presence of nicotine reversed the cytotoxic effect induced by paclitaxel by involving the expression of functional α7 and α9 nAChRs in these cells. The action of nicotine on paclitaxel treatment was linked to the modulation of the protein kinase C, mitogen-activated protein kinase, extracellular signal-regulated kinase, and NF-B signaling pathways, and to an up-regulation of ABCG2 protein expression. We also detected that nicotine significantly reduced the increase in cell apoptosis induced by paclitaxel treatment. Moreover, we observed that the presence of nicotine reduced the efficacy of paclitaxel treatment administered in three cycles to MDA-MB231 tumor cells. CONCLUSIONOur findings point to nAChRs as responsible for the decrease in the chemotherapeutic effect of paclitaxel in triple negative tumors. Thus, they should be considered as targets in smoking patients.
publishDate 2022
dc.date.none.fl_str_mv 2022-04
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info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/215595
Español, Alejandro Javier; Sanchez, Yamila; Salem, Agustina Reina; Obregon, Jaqueline; Sales, María Elena; Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells; Baishideng Publishing Group Inc.; World Journal of Clinical Oncology; 13; 6; 4-2022; 505-519
2218-4333
CONICET Digital
CONICET
url http://hdl.handle.net/11336/215595
identifier_str_mv Español, Alejandro Javier; Sanchez, Yamila; Salem, Agustina Reina; Obregon, Jaqueline; Sales, María Elena; Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells; Baishideng Publishing Group Inc.; World Journal of Clinical Oncology; 13; 6; 4-2022; 505-519
2218-4333
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Baishideng Publishing Group Inc.
publisher.none.fl_str_mv Baishideng Publishing Group Inc.
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