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dc.contributor.author
Díaz Bessone, María Inés
dc.contributor.author
Berardi, Damian Emilio
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Campodónico, Paola Bernadette
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Todaro, Laura Beatriz
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Lothstein, Leonard
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Bal, Elisa Dora
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Urtreger, Alejandro Jorge
dc.date.available
2019-01-03T13:13:22Z
dc.date.issued
2011-04
dc.identifier.citation
Díaz Bessone, María Inés; Berardi, Damian Emilio; Campodónico, Paola Bernadette; Todaro, Laura Beatriz; Lothstein, Leonard; et al.; Involvement of PKC delta (PKCδ) in the resistance against different doxorubicin analogs; Springer; Breast Cancer Research and Treatment; 126; 3; 4-2011; 577-587
dc.identifier.issn
0167-6806
dc.identifier.uri
http://hdl.handle.net/11336/67272
dc.description.abstract
Doxorubicin is an anti-tumor antibiotic widely used in the management of cancer patients. Its main mechanism of action involves the generation of DNA damage and the inhibition of topoisomerase II, promoting apoptosis. AD 198 is a novel doxorubicin analog devoid of DNA binding and topoisomerase II inhibitory capacities. It has been proposed that AD 198 induces apoptosis by activating protein kinase C delta (PKCδ); a PKC isoform described as growth inhibitory in a large number of cell types. We have previously demonstrated that PKCδ over-expression in NMuMG cells induced the opposite effect, promoting proliferation and cell survival. In this study, we found that PKCδ overexpression confers an enhanced cell death resistance against AD 198 cytotoxic effect and against AD 288, another doxorubicin analog that preserves its mechanism of action. These resistances involve PKCδ-mediated activation of two well-known survival pathways: Akt and NF-κB. While the resistance against AD 198 could be abrogated upon the inhibition of either Akt or NF-κB pathways, only NF-κB inhibition could revert the resistance to AD 288. Altogether, our results indicate that PKCδ increases cell death resistance against different apoptosis inductors, independently of their mechanism of action, through a differential modulation of Akt and NF-κB pathways. Our study contributes to a better understanding of the mechanisms involved in PKCδ-induced resistance and may greatly impact in the rationale design of isozyme-specific PKC modulators as therapeutic agents. © Springer Science+Business Media, LLC. 2010.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Ad 198
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Ad 288
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Cell Death Resistance
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PkcΔ
dc.subject.classification
Salud Ocupacional
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Ciencias de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Involvement of PKC delta (PKCδ) in the resistance against different doxorubicin analogs
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-01-02T19:57:17Z
dc.journal.volume
126
dc.journal.number
3
dc.journal.pagination
577-587
dc.journal.pais
Países Bajos
dc.journal.ciudad
Dordrecht
dc.description.fil
Fil: Díaz Bessone, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
dc.description.fil
Fil: Berardi, Damian Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
dc.description.fil
Fil: Campodónico, Paola Bernadette. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
dc.description.fil
Fil: Todaro, Laura Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
dc.description.fil
Fil: Lothstein, Leonard. The University of Tennessee Health Science Center and Center for Cancer Research; Estados Unidos
dc.description.fil
Fil: Bal, Elisa Dora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
dc.description.fil
Fil: Urtreger, Alejandro Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
dc.journal.title
Breast Cancer Research and Treatment
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1007/s10549-010-0956-2
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s10549-010-0956-2


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