Attenuation of tumor burden in response to rucaparib in lung aAdenocarcinoma: the contribution of oxidative stress, apoptosis, and DNA damage

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• dc.contributor.author Pérez-Peiró, Maria
• dc.contributor.author Valentí-Serra, Paula
• dc.contributor.author León-González, Blanca
• dc.contributor.author Ampurdanés, Coral
• dc.contributor.author Duran, Xavier
• dc.contributor.author Yélamos, José
• dc.contributor.author Barreiro Portela, Esther
• dc.date.accessioned 2023-06-20T06:22:41Z
• dc.date.available 2023-06-20T06:22:41Z
• dc.date.issued 2023
• dc.description.abstract In cancer, overactivation of poly (ADPribose) polymerases (PARP) plays a relevant role in DNA repair. We hypothesized that treatment with the PARP inhibitor rucaparib may reduce tumor burden via several biological mechanisms (apoptosis and oxidative stress) in mice. In lung tumors (LP07 lung adenocarcinoma) of mice treated/non-treated (control animals) with PARP inhibitor (rucaparib,150 mg/kg body weight/24 h for 20 day), PARP activity and expression, DNA damage, apoptotic nuclei, cell proliferation, and redox balance were measured using immunoblotting and immunohistochemistry. In lung tumors of rucaparib-treated mice compared to non-treated animals, tumor burden, PARP activity, and cell proliferation decreased, while DNA damage, TUNEL-positive nuclei, protein oxidation, and superoxide dismutase content (SOD)2 increased. In this experiment on lung adenocarcinoma, the pharmacological PARP inhibitor rucaparib elicited a significant improvement in tumor size, probably through a reduction in cell proliferation as a result of a rise in DNA damage and apoptosis. Oxidative stress and SOD2 also increased in response to treatment with rucaparib within the tumor cells of the treated mice. These results put the line forward to the contribution of PARP inhibitors to reduced tumor burden in lung adenocarcinoma. The potential implications of these findings should be tested in clinical settings of patients with lung tumors.
• dc.description.sponsorship This study has been funded by Instituto de Salud Carlos III through the project “FI19/00001” (Co-funded by European Social Fund “Investing in your future”). María Pérez-Peiró was a recipient of a predoctoral fellowship from FIS Contratos Predoctorales de Formación en Investigación en Salud. The current research has been supported by project FIS 18/00075 funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union and Consorcio Centro de Investigación Biomédica en Red (CIBERES) 2022 funded by Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation and European Union; Spanish Respiratory Society (SEPAR), contract grant numbers, SEPAR 2018. The Yélamos lab is funded by the Spanish Ministry of Science and Innovation (grant PID2020-112526RB-I00 funded by MCIN/AEI/10.13039/501100011033).
• dc.format.mimetype application/pdf
• dc.identifier.citation Pérez-Peiró M, Valentí-Serra P, León-González B, Ampurdanés C, Duran X, Yélamos J, et al. Attenuation of tumor burden in response to rucaparib in lung aAdenocarcinoma: the contribution of oxidative stress, apoptosis, and DNA damage. IJMS. 2023 Feb 1;24(3):2580. DOI: 10.3390/ijms24032580
• dc.identifier.doi http://dx.doi.org/10.3390/ijms24032580
• dc.identifier.issn 1661-6596
• dc.identifier.uri http://hdl.handle.net/10230/57252
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof International Journal of Molecular Sciences. 2023 Feb 1;24(3):2580
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-112526RB-I00
• dc.rights © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Lung adenocarcinoma experimental model
• dc.subject.keyword PARP inhibitor rucaparib
• dc.subject.keyword DNA damage and apoptosis
• dc.subject.keyword Cell proliferation
• dc.subject.keyword PARP activity
• dc.subject.keyword Protein oxidation
• dc.subject.keyword Antioxidants
• dc.title Attenuation of tumor burden in response to rucaparib in lung aAdenocarcinoma: the contribution of oxidative stress, apoptosis, and DNA damage
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion