Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/226578
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Bespoken nanoceria: An effective treatment in experimental hepatocellular carcinoma |
Autor: | Fernández-Varo, Guillermo; Perramón, Meritxell; Carvajal, Silvia; Oró, Denise; Casals, Eudald CSIC ORCID; Boix, Loreto; Oller, Laura; Macías‐Muñoz, Laura; Marfà, Santi; Casals, Gregori; Morales-Ruiz, Manuel; Casado, Pedro; Cutillas, Pedro; Bruix, Jordi; Navasa, Miquel; Fuster, Josep; García-Valdecasas, Juan Carlos; Pavel, Mihai C.; Puntes, Víctor F. CSIC ORCID; Jiménez, Wladimiro | Fecha de publicación: | 2020 | Editor: | Wiley-VCH | Citación: | Hepatology 72(4): 1267-1282 (2020) | Resumen: | [Background and Aims]: Despite the availability of new‐generation drugs, hepatocellular carcinoma (HCC) is still the third most frequent cause of cancer‐related deaths worldwide. Cerium oxide nanoparticles (CeO2NPs) have emerged as an antioxidant agent in experimental liver disease because of their antioxidant, anti‐inflammatory, and antisteatotic properties. In the present study, we aimed to elucidate the potential of CeO2NPs as therapeutic agents in HCC. [Approach and Results]: HCC was induced in 110 Wistar rats by intraperitoneal administration of diethylnitrosamine for 16 weeks. Animals were treated with vehicle or CeO2NPs at weeks 16 and 17. At the eighteenth week, nanoceria biodistribution was assessed by mass spectrometry (MS). The effect of CeO2NPs on tumor progression and animal survival was investigated. Hepatic tissue MS‐based phosphoproteomics as well as analysis of principal lipid components were performed. The intracellular uptake of CeO2NPs by human ex vivo perfused livers and human hepatocytes was analyzed. Nanoceria was mainly accumulated in the liver, where it reduced macrophage infiltration and inflammatory gene expression. Nanoceria treatment increased liver apoptotic activity, while proliferation was attenuated. Phosphoproteomic analysis revealed that CeO2NPs affected the phosphorylation of proteins mainly related to cell adhesion and RNA splicing. CeO2NPs decreased phosphatidylcholine‐derived arachidonic acid and reverted the HCC‐induced increase of linoleic acid in several lipid components. Furthermore, CeO2NPs reduced serum alpha‐protein levels and improved the survival of HCC rats. Nanoceria uptake by ex vivo perfused human livers and in vitro human hepatocytes was also demonstrated. [Conclusions]: These data indicate that CeO2NPs partially revert the cellular mechanisms involved in tumor progression and significantly increase survival in HCC rats, suggesting that they could be effective in patients with HCC. |
Versión del editor: | https://doi.org/10.1002/hep.31139 | URI: | http://hdl.handle.net/10261/226578 | DOI: | 10.1002/hep.31139 | ISSN: | 1527-3350 |
Aparece en las colecciones: | (CIN2) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
bespokcarcin.pdf | 1,95 MB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
19
checked on 23-abr-2024
SCOPUSTM
Citations
38
checked on 23-abr-2024
WEB OF SCIENCETM
Citations
33
checked on 25-feb-2024
Page view(s)
124
checked on 22-abr-2024
Download(s)
95
checked on 22-abr-2024