Regulation of cell death receptor S-nitrosylation and apoptotic signaling by Sorafenib in hepatoblastoma cells
| العنوان: | Regulation of cell death receptor S-nitrosylation and apoptotic signaling by Sorafenib in hepatoblastoma cells |
|---|---|
| المؤلفون: | G. Suárez-Artacho, J. Serrano-Díaz-Canedo, Sheila Pereira, G. Blanco-Fernández, C.A. Padilla, L.M. Marín-Gómez, Raúl González, L. Barrera-Pulido, D. Pacheco, Miguel Ángel Gómez-Bravo, M.A. Torres-Nieto, A. Nogales-Muñoz, Elena Navarro-Villarán, F.J. Padillo, J.M. Álamo-Martínez, A. Gila-Bohórquez, C. Bernal-Bellido, José Antonio Bárcena, A. Sarrias-Giménez, L.B. Soriano-De Castro, A. Rodríguez-Hernández, A. Serrablo-Requejo, Jordi Muntané |
| المساهمون: | [Rodríguez-Hernández,A, Navarro-Villarán,E, Pereira,S, Soriano-De Castro,LB, Sarrias-Giménez,A] Institute of Biomedicine of Seville (IBiS), Hospital Universitario 'Virgen del Rocío'/CSIC/Universidad de Sevilla, Sevilla, Spain. [González,R, Barcena,JA, Padilla,CA] Departament of Biochemistry and Molecular Biology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain. [Barrera-Pulido,L, Álamo-Martínez,JM, Nogales-Muñoz,A, Gila-Bohórquez,A, Serrano-Díaz-Canedo,J, Suárez-Artacho,G, Bernal-Bellido,C, Marín-Gómez,LM, Gómez-Bravo,MA, Padillo,FJ, 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. [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. [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. [Álamo-Martínez,JM, Muntané,J] CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain., We thank the Instituto de Salud Carlos III (PI13/00021), Spanish Ministry of Economy and Competitiveness (BFU2012-32056), Consejería Economía, Innovación, Ciencia y Empleo, Junta de An- dalucia (BIO-0216 and CTS-6264) and Consejería de Salud (PI13/ 00025) for its financial support. We thank Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd) founded by Instituto de Salud Carlos III., Universidad de Sevilla. Departamento de Cirugía, Universidad de Sevilla. CTS664: Cirugía Avanzada y Trasplantes. Terapia Celular y Bioingeniería Aplicada a la Cirugía |
| المصدر: | Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid Redox Biology idUS. Depósito de Investigación de la Universidad de Sevilla instname |
| بيانات النشر: | Elsevier, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Hepatoblastoma, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Complex and Mixed::Hepatoblastoma [Medical Subject Headings], Neoplasias Hepáticas, Receptor expression, Clinical Biochemistry, Apoptosis, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Cysteine Proteases::Cysteine Endopeptidases::Caspases::Caspases, Effector::Caspase 3 [Medical Subject Headings], Chemicals and Drugs::Organic Chemicals::Urea::Phenylurea Compounds [Medical Subject Headings], Biochemistry, TNF-R1, tumor necrosis factor receptor type I, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Carcinoma, Hepatocellular [Medical Subject Headings], Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Cysteine Proteases::Cysteine Endopeptidases::Caspases::Caspases, Initiator::Caspase 8 [Medical Subject Headings], FADD, Receptor, NOS, nitric oxide synthase, Caspase 8, Cell Death, Caspase 3, Caspasa 8, Chemicals and Drugs::Inorganic Chemicals::Free Radicals::Nitric Oxide [Medical Subject Headings], Hep G2 Cells, CSNO, S-nitroso-l-cysteine, Sorafenib, Caspase 9, Cell biology, Gene Expression Regulation, Neoplastic, Receptors, Tumor Necrosis Factor, Type I, H2O2, hydrogen peroxide, Anatomy::Cells::Cells, Cultured::Tumor Cells, Cultured::Cell Line, Tumor::Hep G2 Cells [Medical Subject Headings], Signal transduction, Chemicals and Drugs::Heterocyclic Compounds::Acids, Heterocyclic::Nicotinic Acids::Niacinamide [Medical Subject Headings], medicine.drug, Research Paper, Signal Transduction, Niacinamide, Programmed cell death, Nitric Oxide Synthase Type III, TRAIL-R1, tumor necrosis factor-related apoptosis-inducing ligand type I, Muerte Celular, Diseases::Digestive System Diseases::Digestive System Neoplasms::Liver Neoplasms [Medical Subject Headings], Antineoplastic Agents, Biology, Nitric Oxide, NO, medicine, Death-receptors, Humans, Caspasa 3, Nitric Oxide Donors, Cysteine, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Nitric Oxide Donors [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Death Domain [Medical Subject Headings], FADD, Fas-associated death domain, NO, nitric oxide, S-Nitrosothiols, Óxido Nítrico, NONOate, 1,1-diethyl-2-hydroxy-2-nitroso-hydrazine sodium, Phenylurea Compounds, Organic Chemistry, Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death [Medical Subject Headings], digestive system diseases, S-nitrosylation, Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis [Medical Subject Headings], Receptors, TNF-Related Apoptosis-Inducing Ligand, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on CH-NH2 Group Donors::Amino Acid Oxidoreductases::Nitric Oxide Synthase::Nitric Oxide Synthase Type III [Medical Subject Headings], biology.protein, Cancer research, DAF-FM, 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate, O2·−, superoxide anion, Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Damage::DNA Fragmentation [Medical Subject Headings], Compuestos de Fenilurea |
| الوصف: | 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 (10 nM) 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. Graphical abstract Highlights • Sorafenib induces apoptosis in hepatoblastoma cells. • Low concentration of Sorafenib (10 nM) increases the expression of cell death receptor, as well as caspase-8 and -9 activation. • High concentration of Sorafenib (10 µM) reduced cell death receptor S-nitrosylation that promoted a shift to more potent activation of downstream apoptotic markers. |
| وصف الملف: | application/pdf |
| اللغة: | Spanish; Castilian |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::429b6e36ed61083a2525dbb900b9fc31 https://hdl.handle.net/10668/2005 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....429b6e36ed61083a2525dbb900b9fc31 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |