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Artículo

P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach

Joray, Mariana BelénIcon ; Villafañez, Florencia; González, María Laura; Crespo, Maria InesIcon ; Laiolo, JerónimoIcon ; Palacios, Sara MariaIcon ; Bocco, Jose LuisIcon ; Soria, Ramiro GastonIcon ; Carpinella, Maria CeciliaIcon
Fecha de publicación: 29/11/2017
Editorial: Pergamon-Elsevier Science Ltd
Revista: Food And Chemical Toxicology
ISSN: 0278-6915
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Farmacología y Farmacia

Resumen

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.
Palabras clave: Meliartenin12 , Hydroxyamoorastatin , Cytotoxicity , Apoptosis , Cell Cycle Arrest , Hct116 , P53
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)
Identificadores
URI: http://hdl.handle.net/11336/47796
URL: https://www.sciencedirect.com/science/article/pii/S027869151730217X
DOI: https://dx.doi.org/10.1016/j.fct.2017.04.039
Colecciones
Articulos(CCT - CORDOBA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - CORDOBA
Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos(IRNASUS)
Articulos de INSTITUTO DE INVESTIGACIONES EN RECURSOS NATURALES Y SUSTENTABILIDAD JOSE SANCHEZ LABRADOR S.J.
Citación
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
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