dc.creator | López-Grueso, María José | es |
dc.creator | González, Raúl | es |
dc.creator | Muntané Relat, Jordi | es |
dc.creator | Bárcena, José Antonio | es |
dc.creator | Padilla, C. Alicia | es |
dc.date.accessioned | 2020-09-10T15:58:55Z | |
dc.date.available | 2020-09-10T15:58:55Z | |
dc.date.issued | 2019-10-22 | |
dc.identifier.citation | López-Grueso, M.J., González, R., Muntané Relat, J., Bárcena, J.A. y Padilla, C.A. (2019). Thioredoxin Downregulation Enhances Sorafenib Effects in Hepatocarcinoma Cells. Antioxidants, 8 (10), 501-. | |
dc.identifier.issn | 2076-3921 | es |
dc.identifier.uri | https://hdl.handle.net/11441/100926 | |
dc.description.abstract | Sorafenib is the first-line recommended therapy for patients with advanced hepatocarcinoma
(HCC) in de-differentiation stage (presenting epithelial–mesenchymal transition, EMT). We studied
the role of the thioredoxin system (Trx1/TrxR1) in the sensitivity or resistance of HCC cells to the
treatment with Sorafenib. As a model, we used a set of three established HCC cell lines with different
degrees of de-differentiation as occurs in metastasis. By quantitative proteomics, we found that the
expression levels of Trx1 and TrxR1 followed the same trend as canonical EMT markers in these cell
lines. Treatment with Sorafenib induced thiol redox reductive changes in critical elements of oncogenic
pathways in all three cell lines but induced drastic proteome reprograming only in HCC cell lines of
intermediate stage. Trx1 downregulation counteracted the thiol reductive effect of Sorafenib on Signal
Transducer and Activator of Transcription 3 (STAT3) but not on Mitogen-Activated Protein Kinase
(MAPK) or Protein Kinase B (Akt) and transformed advanced HCC cells into Sorafenib-sensitive cells.
Ten targets of the combined Sorafenib–siRNATrx1 treatment were identified that showed a gradually
changing expression trend in parallel to changes in the expression of canonical EMT markers, likely
as a result of the activation of Hippo signaling. These findings support the idea that a combination of
Sorafenib with thioredoxin inhibitors should be taken into account in the design of therapies against
advanced HCC. | es |
dc.description.sponsorship | Ministerio de Economía y Competitividad BFU2016-80006-P | es |
dc.description.sponsorship | Instituto de Salud Carlos III (ISCIII) PI13/00021 y PI16/00090 | es |
dc.description.sponsorship | Junta de Andalucía Consejería de Economía, Innovación, Ciencia y Empleo BIO-0216 y CTS-6264 | es |
dc.description.sponsorship | Junta de Andalucía Consejería de Igualdad, Salud y Políticas Sociales PI-00025-2013 y PI-0198-2016 | es |
dc.format | application/pdf | es |
dc.format.extent | 18 | es |
dc.language.iso | eng | es |
dc.publisher | MDPI | es |
dc.relation.ispartof | Antioxidants, 8 (10), 501-. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Hepatocarcinoma | es |
dc.subject | Thioredoxin | es |
dc.subject | Sorafenib | es |
dc.subject | Redox signaling | es |
dc.subject | EMT | es |
dc.title | Thioredoxin Downregulation Enhances Sorafenib Effects in Hepatocarcinoma Cells | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Cirugía | es |
dc.relation.projectID | BFU2016-80006-P | es |
dc.relation.projectID | PI13/00021 | es |
dc.relation.projectID | PI16/00090 | es |
dc.relation.projectID | BIO-0216 | es |
dc.relation.projectID | CTS-6264 | es |
dc.relation.projectID | PI-00025-2013 | es |
dc.relation.projectID | PI-0198-2016 | es |
dc.identifier.doi | 10.3390/antiox8100501 | es |
dc.journaltitle | Antioxidants | es |
dc.publication.volumen | 8 | es |
dc.publication.issue | 10 | es |
dc.publication.initialPage | 501 | es |