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| Página principal > Artículos > Artículos publicados > Bespoken Nanoceria : |
(Universitat de Barcelona) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Wuyi University) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Working Group for the Biochemical Assessment of Hepatic Disease-SEQC ML) (Barts Cancer Institute (BCI)) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Universitat de Barcelona)| Fecha: | 2020 |
| Resumen: | 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 (CeONPs) 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 CeONPs as therapeutic agents in HCC. HCC was induced in 110 Wistar rats by intraperitoneal administration of diethylnitrosamine for 16 weeks. Animals were treated with vehicle or CeONPs at weeks 16 and 17. At the eighteenth week, nanoceria biodistribution was assessed by mass spectrometry (MS). The effect of CeONPs 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 CeONPs 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 CeONPs affected the phosphorylation of proteins mainly related to cell adhesion and RNA splicing. CeONPs decreased phosphatidylcholine-derived arachidonic acid and reverted the HCC-induced increase of linoleic acid in several lipid components. Furthermore, CeONPs 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. These data indicate that CeONPs 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. |
| Ayudas: | Ministerio de Ciencia e Innovación SAF15-64126-R Ministerio de Ciencia e Innovación SAF2016-75358-R Ministerio de Ciencia e Innovación RTI2018-094734-B-C21 Instituto de Salud Carlos III PI15-00077 Instituto de Salud Carlos III PI18-00763 Instituto de Salud Carlos III PI19-00774 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-2019 |
| Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.  |
| Lengua: | Anglès |
| Documento: | Article ; recerca ; Versió publicada |
| Publicado en: | Hepatology, Vol. 72 (october 2020) , p. 1267-1282, ISSN 1527-3350 |
