Regulation of cell death receptor S-nitrosylation and apoptotic signaling by Sorafenib in hepatoblastoma cells.

Autor:	Rodríguez-Hernández A; Institute of Biomedicine of Seville (IBiS), Hospital Universitario 'Virgen del Rocío'/CSIC/Universidad de Sevilla, Av. Manuel Siurot s/n, 41013 Sevilla, Spain., Navarro-Villarán E; Institute of Biomedicine of Seville (IBiS), Hospital Universitario 'Virgen del Rocío'/CSIC/Universidad de Sevilla, Av. Manuel Siurot s/n, 41013 Sevilla, Spain., González R; Departament of Biochemistry and Molecular Biology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14071 Córdoba, Spain., Pereira S; Institute of Biomedicine of Seville (IBiS), Hospital Universitario 'Virgen del Rocío'/CSIC/Universidad de Sevilla, Av. Manuel Siurot s/n, 41013 Sevilla, Spain., Soriano-De Castro LB; Institute of Biomedicine of Seville (IBiS), Hospital Universitario 'Virgen del Rocío'/CSIC/Universidad de Sevilla, Av. Manuel Siurot s/n, 41013 Sevilla, Spain., Sarrias-Giménez A; Institute of Biomedicine of Seville (IBiS), Hospital Universitario 'Virgen del Rocío'/CSIC/Universidad de Sevilla, Av. Manuel Siurot s/n, 41013 Sevilla, Spain., Barrera-Pulido L; Department of General Surgery, Hospital Universitario 'Virgen del Rocío' - 'Virgen Macarena'/Instituto de Biomedicina de Sevilla (IBiS)/CSIC/Universidad de Sevilla, Sevilla, Spain., Álamo-Martínez JM; Department of General Surgery, Hospital Universitario 'Virgen del Rocío' - 'Virgen Macarena'/Instituto de Biomedicina de Sevilla (IBiS)/CSIC/Universidad de Sevilla, Sevilla, Spain; CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain., Serrablo-Requejo A; Hepato-Biliary Surgery Unit, Hospital Universitario 'Miguel Servet', Zaragoza, Spain., Blanco-Fernández G; Hepato-Biliary-Pancreatic and Liver Transplant Service, Hospital Universitario 'Infanta Cristina', Badajoz, Spain., Nogales-Muñoz A; Department of General Surgery, Hospital Universitario 'Virgen del Rocío' - 'Virgen Macarena'/Instituto de Biomedicina de Sevilla (IBiS)/CSIC/Universidad de Sevilla, Sevilla, Spain., Gila-Bohórquez A; Department of General Surgery, Hospital Universitario 'Virgen del Rocío' - 'Virgen Macarena'/Instituto de Biomedicina de Sevilla (IBiS)/CSIC/Universidad de Sevilla, Sevilla, Spain., Pacheco D; Department of General Surgery and Department of Pathology, Hospital Universitario 'Rio Hortega', Valladolid, Spain., Torres-Nieto MA; Department of Pathology, Hospital Universitario 'Rio Hortega', Valladolid, Spain., Serrano-Díaz-Canedo J; Department of General Surgery, Hospital Universitario 'Virgen del Rocío' - 'Virgen Macarena'/Instituto de Biomedicina de Sevilla (IBiS)/CSIC/Universidad de Sevilla, Sevilla, Spain., Suárez-Artacho G; Department of General Surgery, Hospital Universitario 'Virgen del Rocío' - 'Virgen Macarena'/Instituto de Biomedicina de Sevilla (IBiS)/CSIC/Universidad de Sevilla, Sevilla, Spain., Bernal-Bellido C; Department of General Surgery, Hospital Universitario 'Virgen del Rocío' - 'Virgen Macarena'/Instituto de Biomedicina de Sevilla (IBiS)/CSIC/Universidad de Sevilla, Sevilla, Spain., Marín-Gómez LM; Department of General Surgery, Hospital Universitario 'Virgen del Rocío' - 'Virgen Macarena'/Instituto de Biomedicina de Sevilla (IBiS)/CSIC/Universidad de Sevilla, Sevilla, Spain., Barcena JA; Departament of Biochemistry and Molecular Biology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14071 Córdoba, Spain., Gómez-Bravo MA; Department of General Surgery, Hospital Universitario 'Virgen del Rocío' - 'Virgen Macarena'/Instituto de Biomedicina de Sevilla (IBiS)/CSIC/Universidad de Sevilla, Sevilla, Spain; CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain., Padilla CA; Departament of Biochemistry and Molecular Biology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14071 Córdoba, Spain., Padillo FJ; Department of General Surgery, Hospital Universitario 'Virgen del Rocío' - 'Virgen Macarena'/Instituto de Biomedicina de Sevilla (IBiS)/CSIC/Universidad de Sevilla, Sevilla, Spain; CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain., Muntané J; Department of General Surgery, Hospital Universitario 'Virgen del Rocío' - 'Virgen Macarena'/Instituto de Biomedicina de Sevilla (IBiS)/CSIC/Universidad de Sevilla, Sevilla, Spain; CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. Electronic address: jmuntane-ibis@us.es.
Jazyk:	angličtina
Zdroj:	Redox biology [Redox Biol] 2015 Dec; Vol. 6, pp. 174-182. Date of Electronic Publication: 2015 Jul 22.
DOI:	10.1016/j.redox.2015.07.010
Abstrakt:	Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10 µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells. (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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