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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/215595
Ver los metadatos del registro completo
id |
CONICETDig_e4265ac02a78510c8399eaaa6fa7c8af |
---|---|
oai_identifier_str |
oai:ri.conicet.gov.ar:11336/215595 |
network_acronym_str |
CONICETDig |
repository_id_str |
3498 |
network_name_str |
CONICET Digital (CONICET) |
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 |
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/11336/215595 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 |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.5306/wjco.v13.i6.505 info:eu-repo/semantics/altIdentifier/url/https://www.wjgnet.com/2218-4333/full/v13/i6/505.htm |
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 application/pdf |
dc.publisher.none.fl_str_mv |
Baishideng Publishing Group Inc. |
publisher.none.fl_str_mv |
Baishideng Publishing Group Inc. |
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 |
_version_ |
1844613053949149184 |
score |
13.070432 |