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dc.contributor.author
Wempe, Stacy L.
dc.contributor.author
Gamarra Luques, Carlos Diego
dc.contributor.author
Telleria, Carlos Marcelo
dc.date.available
2016-12-26T15:06:58Z
dc.date.issued
2013-01
dc.identifier.citation
Wempe, Stacy L.; Gamarra Luques, Carlos Diego; Telleria, Carlos Marcelo; Synergistic lethality of mifepristone and LY294002 in ovarian cancer cells; Libertas Academica; Cancer Growth and Metastasis; 6; 1-2013; 1-13
dc.identifier.issn
1179-0644
dc.identifier.uri
http://hdl.handle.net/11336/10083
dc.description.abstract
We have previously shown that the antiprogestin and antiglucocorticoid mifepristone inhibits the growth of ovarian cancer cells. In this work, we hypothesized that cellular stress caused by mifepristone is limited to cytostasis and that cell killing is avoided as a consequence of the persistent activity of the PI3K/Akt survival pathway. To investigate the role of this pathway in mifepristone-induced growth inhibition, human ovarian cancer cells of various histological subtypes and genetic backgrounds were exposed to cytostatic doses of mifepristone in the presence or absence of the PI3K inhibitor, LY294002. The activation of Akt in ovarian cancer cells, as marked by its phosphorylation on Ser473, was not modified by cytostatic concentrations of mifepristone, but it was blocked upon treat¬ment with LY294002. The combination mifepristone/LY294002, but not the individual drugs, killed ovarian cancer cells via apoptosis, as attested by genomic DNA fragmentation and cleavage of caspase-3, and the concomitant downregulation of antiapoptotic proteins Bcl-2 and XIAP. From a pharmacological standpoint, when assessing cell growth inhibition using a median-dose analysis algorithm, the interaction between mifepristone and LY294002 was synergistic. The lethality caused by the combination mifepristone/LY294004 in 2-dimensional cell cultures was recapitulated in organized, 3-dimensional spheroids. This study demonstrates that mifepristone and LY294002 when used individually cause cell growth arrest; yet, when combined, they cause lethality.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Libertas Academica
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Ovarian Cancer
dc.subject
Mifepristone
dc.subject
Ly294002
dc.subject
Sinergism
dc.subject.classification
Farmacología y Farmacia
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Synergistic lethality of mifepristone and LY294002 in ovarian cancer cells
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-09-19T18:46:47Z
dc.journal.volume
6
dc.journal.pagination
1-13
dc.journal.pais
Nueva Zelanda
dc.journal.ciudad
Aukland
dc.description.fil
Fil: Wempe, Stacy L.. The University of South Dakota. Sanford School of Medicine. Division of Basic Biomedical Sciences; Estados Unidos
dc.description.fil
Fil: Gamarra Luques, Carlos Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. The University of South Dakota. Sanford School of Medicine. Division of Basic Biomedical Sciences; Estados Unidos
dc.description.fil
Fil: Telleria, Carlos Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. The University of South Dakota. Sanford School of Medicine. Division of Basic Biomedical Sciences; Estados Unidos
dc.journal.title
Cancer Growth and Metastasis
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.la-press.com/synergistic-lethality-of-mifepristone-and-ly294002-in-ovarian-cancer-c-article-a3496
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.4137/CGM.S11124


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