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dc.contributor.author
Joray, Mariana Belén
dc.contributor.author
Villafañez, Florencia
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González, María Laura
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Crespo, Maria Ines
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Laiolo, Jerónimo
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Palacios, Sara Maria
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Bocco, Jose Luis
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Soria, Ramiro Gaston
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Carpinella, Maria Cecilia
dc.date.available
2018-06-07T20:57:02Z
dc.date.issued
2017-11-29
dc.identifier.citation
Joray, Mariana Belén; Villafañez, Florencia; González, María Laura; Crespo, Maria Ines; Laiolo, Jerónimo; et al.; P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach; Pergamon-Elsevier Science Ltd; Food And Chemical Toxicology; 109; Part 2; 29-11-2017; 888-897
dc.identifier.issn
0278-6915
dc.identifier.uri
http://hdl.handle.net/11336/47796
dc.description.abstract
This work examines the antitumor activity of an isomeric mixture (1), composed of the limonoids meliartenin and its interchangeable isomer 12-hydroxyamoorastatin. The results obtained showed that 1 displayed outstanding cytotoxic activity against CCRF-CEM, K562, A549 and HCT116 cells, with a highly selective effect on the latter, with an IC50 value of 0.2 μM. Based on this finding, HCT116 cells were selected to study the mechanism of action of 1. Cell cycle analysis revealed that 1 induced sustained arrest in the S-phase, which was followed by the triggering of apoptotic cell death and reduced clonogenic capacity. This cytotoxicity was seen to be preceded by the upregulation of the tumor suppressor p53 and its target effector p21. In addition, it was found that p53 expression was required for efficient cell death induction, and thus that the toxicity of 1 relies mainly on p53-dependent mechanisms. Taken together, these findings position 1 as a potent antitumor agent, with potential for the development of novel chemotherapeutic drugs based on the induction of S-phase arrest.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Pergamon-Elsevier Science Ltd
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Meliartenin12
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Hydroxyamoorastatin
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Cytotoxicity
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Apoptosis
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Cell Cycle Arrest
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Hct116
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P53
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Farmacología y Farmacia
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-05-30T17:20:32Z
dc.journal.volume
109
dc.journal.number
Part 2
dc.journal.pagination
888-897
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Joray, Mariana Belén. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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Fil: Villafañez, Florencia. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: González, María Laura. Universidad Católica de Córdoba; Argentina
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Fil: Crespo, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Católica de Córdoba; Argentina
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Fil: Laiolo, Jerónimo. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Palacios, Sara Maria. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Bocco, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Soria, Ramiro Gaston. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.journal.title
Food And Chemical Toxicology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S027869151730217X
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1016/j.fct.2017.04.039
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