Involvement of alpha2 and beta2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation

Autores
Perez, Cecilia; Bruzzone, Ariana; Sarappa, M. G.; Castillo, L. F.; Luthy, Isabel Alicia
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background and purpose: Beta-adrenoceptor (B-AR) expression is known in human and experimental animal breast cancer cells. However, the effect of the agonists and antagonists reported on cell proliferation and tumour growth was paradoxical, precluding the utilization as possible adjuvant therapy, mainly in the cases of refractory tumours. Experimental approach: The expression of B-AR was analysed by immunofluorescence and RT-PCR. Cell proliferation was assessed by [(3) H]-thymidine incorporation, tumour growth by measuring with a calliper and Erk 1/2 phosphorylation by western blotting. Key results: B2 -AR expression was confirmed in the mouse and human cells tested. Cell proliferation was increased by epinephrine (by alpha(2)-AR action) and decreased in every tested cell line by the B-agonist isoproterenol and the B2-agonist salbutamol. Isoproterenol and salbutamol reduced tumour growth in every tumour tested (mouse C4-HD and CC4-3-HI and human IBH-4, IBH-6 and MDA-MB-231 cell lines growing as xenografts in nude mice). This effect was reversed by the B-adrenergic antagonist propranolol. The alpha2-adrenergic antagonist rauwolscine and the B2-adrenergic agonist salbutamol performed equally well in diminishing tumour growth. Erk 1/2 activation analysed in IBH-4 tumours perfectly matched tumour growth, with the B-adrenergic agonists lowering its activation. Erk 1/2 phosphorylation inhibition in vitro was mainly mediated by the PKA pathway. Conclusions and Implications: In the experimental models studied, the B-adrenergic agonists inhibit breast cancer cell proliferation and tumour growth. This effect is probably mediated by Erk 1/2 phosphorylation inhibition. The B-adrenergic agonists perform equally well as the alpha2-adrenergic antagonist rauwolscine, providing possible novel therapeutic adjuvant treatments for breast cancer.
Fil: Perez, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Sarappa, M. G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Castillo, L. F.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Materia
Mammary
Tumour
Salbutamol
Isoprenaline
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:11336/8775
Acceder
id CONICETDig_41619cb1e5dea4f3c7a33449a1dcf282
oai_identifier_str oai:ri.conicet.gov.ar:11336/8775
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Involvement of alpha2 and beta2-adrenoceptors on breast cancer cell proliferation and tumour growth regulationPerez, CeciliaBruzzone, ArianaSarappa, M. G.Castillo, L. F.Luthy, Isabel AliciaMammaryTumourSalbutamolIsoprenalinehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background and purpose: Beta-adrenoceptor (B-AR) expression is known in human and experimental animal breast cancer cells. However, the effect of the agonists and antagonists reported on cell proliferation and tumour growth was paradoxical, precluding the utilization as possible adjuvant therapy, mainly in the cases of refractory tumours. Experimental approach: The expression of B-AR was analysed by immunofluorescence and RT-PCR. Cell proliferation was assessed by [(3) H]-thymidine incorporation, tumour growth by measuring with a calliper and Erk 1/2 phosphorylation by western blotting. Key results: B2 -AR expression was confirmed in the mouse and human cells tested. Cell proliferation was increased by epinephrine (by alpha(2)-AR action) and decreased in every tested cell line by the B-agonist isoproterenol and the B2-agonist salbutamol. Isoproterenol and salbutamol reduced tumour growth in every tumour tested (mouse C4-HD and CC4-3-HI and human IBH-4, IBH-6 and MDA-MB-231 cell lines growing as xenografts in nude mice). This effect was reversed by the B-adrenergic antagonist propranolol. The alpha2-adrenergic antagonist rauwolscine and the B2-adrenergic agonist salbutamol performed equally well in diminishing tumour growth. Erk 1/2 activation analysed in IBH-4 tumours perfectly matched tumour growth, with the B-adrenergic agonists lowering its activation. Erk 1/2 phosphorylation inhibition in vitro was mainly mediated by the PKA pathway. Conclusions and Implications: In the experimental models studied, the B-adrenergic agonists inhibit breast cancer cell proliferation and tumour growth. This effect is probably mediated by Erk 1/2 phosphorylation inhibition. The B-adrenergic agonists perform equally well as the alpha2-adrenergic antagonist rauwolscine, providing possible novel therapeutic adjuvant treatments for breast cancer.Fil: Perez, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Sarappa, M. G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Castillo, L. F.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentinawiley2012-04-13info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/8775Perez, Cecilia; Bruzzone, Ariana; Sarappa, M. G.; Castillo, L. F.; Luthy, Isabel Alicia; Involvement of alpha2 and beta2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation; wiley; British Journal Of Pharmacology; 166; 2; 13-4-2012; 721-7360007-11881476-5381enginfo:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1111/j.1476-5381.2011.01791.xinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417500/info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01791.x/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 Técnicas2025-10-22T11:24:49Zoai:ri.conicet.gov.ar:11336/8775instacron: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:34982025-10-22 11:24:49.549CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Involvement of alpha2 and beta2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation
title Involvement of alpha2 and beta2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation
spellingShingle Involvement of alpha2 and beta2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation
Perez, Cecilia
Mammary
Tumour
Salbutamol
Isoprenaline
title_short Involvement of alpha2 and beta2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation
title_full Involvement of alpha2 and beta2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation
title_fullStr Involvement of alpha2 and beta2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation
title_full_unstemmed Involvement of alpha2 and beta2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation
title_sort Involvement of alpha2 and beta2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation
dc.creator.none.fl_str_mv Perez, Cecilia
Bruzzone, Ariana
Sarappa, M. G.
Castillo, L. F.
Luthy, Isabel Alicia
author Perez, Cecilia
author_facet Perez, Cecilia
Bruzzone, Ariana
Sarappa, M. G.
Castillo, L. F.
Luthy, Isabel Alicia
author_role author
author2 Bruzzone, Ariana
Sarappa, M. G.
Castillo, L. F.
Luthy, Isabel Alicia
author2_role author
author
author
author
dc.subject.none.fl_str_mv Mammary
Tumour
Salbutamol
Isoprenaline
topic Mammary
Tumour
Salbutamol
Isoprenaline
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 and purpose: Beta-adrenoceptor (B-AR) expression is known in human and experimental animal breast cancer cells. However, the effect of the agonists and antagonists reported on cell proliferation and tumour growth was paradoxical, precluding the utilization as possible adjuvant therapy, mainly in the cases of refractory tumours. Experimental approach: The expression of B-AR was analysed by immunofluorescence and RT-PCR. Cell proliferation was assessed by [(3) H]-thymidine incorporation, tumour growth by measuring with a calliper and Erk 1/2 phosphorylation by western blotting. Key results: B2 -AR expression was confirmed in the mouse and human cells tested. Cell proliferation was increased by epinephrine (by alpha(2)-AR action) and decreased in every tested cell line by the B-agonist isoproterenol and the B2-agonist salbutamol. Isoproterenol and salbutamol reduced tumour growth in every tumour tested (mouse C4-HD and CC4-3-HI and human IBH-4, IBH-6 and MDA-MB-231 cell lines growing as xenografts in nude mice). This effect was reversed by the B-adrenergic antagonist propranolol. The alpha2-adrenergic antagonist rauwolscine and the B2-adrenergic agonist salbutamol performed equally well in diminishing tumour growth. Erk 1/2 activation analysed in IBH-4 tumours perfectly matched tumour growth, with the B-adrenergic agonists lowering its activation. Erk 1/2 phosphorylation inhibition in vitro was mainly mediated by the PKA pathway. Conclusions and Implications: In the experimental models studied, the B-adrenergic agonists inhibit breast cancer cell proliferation and tumour growth. This effect is probably mediated by Erk 1/2 phosphorylation inhibition. The B-adrenergic agonists perform equally well as the alpha2-adrenergic antagonist rauwolscine, providing possible novel therapeutic adjuvant treatments for breast cancer.
Fil: Perez, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Sarappa, M. G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Castillo, L. F.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
description Background and purpose: Beta-adrenoceptor (B-AR) expression is known in human and experimental animal breast cancer cells. However, the effect of the agonists and antagonists reported on cell proliferation and tumour growth was paradoxical, precluding the utilization as possible adjuvant therapy, mainly in the cases of refractory tumours. Experimental approach: The expression of B-AR was analysed by immunofluorescence and RT-PCR. Cell proliferation was assessed by [(3) H]-thymidine incorporation, tumour growth by measuring with a calliper and Erk 1/2 phosphorylation by western blotting. Key results: B2 -AR expression was confirmed in the mouse and human cells tested. Cell proliferation was increased by epinephrine (by alpha(2)-AR action) and decreased in every tested cell line by the B-agonist isoproterenol and the B2-agonist salbutamol. Isoproterenol and salbutamol reduced tumour growth in every tumour tested (mouse C4-HD and CC4-3-HI and human IBH-4, IBH-6 and MDA-MB-231 cell lines growing as xenografts in nude mice). This effect was reversed by the B-adrenergic antagonist propranolol. The alpha2-adrenergic antagonist rauwolscine and the B2-adrenergic agonist salbutamol performed equally well in diminishing tumour growth. Erk 1/2 activation analysed in IBH-4 tumours perfectly matched tumour growth, with the B-adrenergic agonists lowering its activation. Erk 1/2 phosphorylation inhibition in vitro was mainly mediated by the PKA pathway. Conclusions and Implications: In the experimental models studied, the B-adrenergic agonists inhibit breast cancer cell proliferation and tumour growth. This effect is probably mediated by Erk 1/2 phosphorylation inhibition. The B-adrenergic agonists perform equally well as the alpha2-adrenergic antagonist rauwolscine, providing possible novel therapeutic adjuvant treatments for breast cancer.
publishDate 2012
dc.date.none.fl_str_mv 2012-04-13
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/11336/8775
Perez, Cecilia; Bruzzone, Ariana; Sarappa, M. G.; Castillo, L. F.; Luthy, Isabel Alicia; Involvement of alpha2 and beta2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation; wiley; British Journal Of Pharmacology; 166; 2; 13-4-2012; 721-736
0007-1188
1476-5381
url http://hdl.handle.net/11336/8775
identifier_str_mv Perez, Cecilia; Bruzzone, Ariana; Sarappa, M. G.; Castillo, L. F.; Luthy, Isabel Alicia; Involvement of alpha2 and beta2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation; wiley; British Journal Of Pharmacology; 166; 2; 13-4-2012; 721-736
0007-1188
1476-5381
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1111/j.1476-5381.2011.01791.x
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417500/
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01791.x/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 wiley
publisher.none.fl_str_mv wiley
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 12.982451

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