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dc.contributor.author
Nuñez, Mariel Alejandra
dc.contributor.author
Medina, Vanina Araceli
dc.contributor.author
Cricco, Graciela Patricia
dc.contributor.author
Croci, Máximo
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Cocca, Claudia Marcela
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Rivera, Elena
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Bergoc, Rosa Maria
dc.contributor.author
Martin, Gabriela Adriana
dc.date.available
2017-05-17T20:27:27Z
dc.date.issued
2013-01
dc.identifier.citation
Nuñez, Mariel Alejandra; Medina, Vanina Araceli; Cricco, Graciela Patricia; Croci, Máximo; Cocca, Claudia Marcela; et al.; Glibenclamide inhibits cell growth by inducing G0/G1 arrest in the human breast cancer cell line MDA-MB-231; BioMed Central; BMC Pharmacology and Toxicology; 14; 6; 1-2013; 1-13
dc.identifier.issn
2050-6511
dc.identifier.uri
http://hdl.handle.net/11336/16591
dc.description.abstract
Background: Glibenclamide (Gli) binds to the sulphonylurea receptor (SUR) that is a regulatory subunit of ATP-sensitive potassium channels (KATP channels). Binding of Gli to SUR produces the closure of KATP channels and the inhibition of their activity. This drug is widely used for treatment of type 2-diabetes and it has been signaled as antiproliferative in several tumor cell lines. In previous experiments we demonstrated the antitumoral effect of Gli in mammary tumors induced in rats. The aim of the present work was to investigate the effect of Gli on MDA-MB-231 breast cancer cell proliferation and to examine the possible pathways involved in this action. Results: The mRNA expression of the different subunits that compose the KATP channels was evaluated in MDA-MB-231 cells by reverse transcriptase-polymerase chain reaction. Results showed the expression of mRNA for both pore-forming isoforms Kir6.1 and Kir6.2 and for the regulatory isoform SUR2B in this cell line. Gli inhibited cell proliferation assessed by a clonogenic method in a dose dependent manner, with an increment in the population doubling time. The KATP channel opener minoxidil increased clonogenic proliferation, effect that was counteracted by Gli. When cell cycle analysis was performed by flow cytometry, Gli induced a significant cell-cycle arrest in G0/G1 phase, together with an up-regulation of p27 levels and a diminution in cyclin E expression, both evaluated by immunoblot. However, neither differentiation evaluated by neutral lipid accumulation nor apoptosis assessed by different methodologies were detected. The cytostatic, non toxic effect on cell proliferation was confirmed by removal of the drug. Combination treatment of Gli with tamoxifen or doxorubicin showed an increment in the antiproliferative effect only for doxorubicin. Conclusions: Our data clearly demonstrated a cytostatic effect of Gli in MDA-MB-231 cells that may be mediated through KATP channels, associated to the inhibition of the G1-S phase progression. In addition, an interesting observation about the effect of the combination of Gli with doxorubicin leads to future research for a potentialnovel role for Gli as an adjuvant in breast cancer treatment.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
BioMed Central
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
Glibenclamide
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Potassium Channels
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Mda-Mb-231
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Cytostatic Effect
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Oncología
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Medicina Clínica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Glibenclamide inhibits cell growth by inducing G0/G1 arrest in the human breast cancer cell line MDA-MB-231
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-05-15T14:43:42Z
dc.journal.volume
14
dc.journal.number
6
dc.journal.pagination
1-13
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: Nuñez, Mariel Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Medina, Vanina Araceli. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Cricco, Graciela Patricia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Croci, Máximo. Instituto de Inmuno Oncología "Dr. Ernesto J. V. Crescenti"; Argentina
dc.description.fil
Fil: Cocca, Claudia Marcela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Rivera, Elena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
dc.description.fil
Fil: Bergoc, Rosa Maria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Instituto Universidad de la Fundación "Héctor Barceló"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Martin, Gabriela Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
dc.journal.title
BMC Pharmacology and Toxicology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/2050-6511-14-6
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1186/2050-6511-14-6
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