Attenuation of muscle damage, structural abnormalities, and physical activity in respiratory and limb muscles following treatment with rucaparib in lung cancer cachexia mice

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  • dc.contributor.author Pérez-Peiró, Maria
  • dc.contributor.author Duran Jordà, Xavier, 1974-
  • dc.contributor.author Yélamos López, José
  • dc.contributor.author Barreiro Portela, Esther
  • dc.date.accessioned 2023-07-07T06:51:48Z
  • dc.date.available 2023-07-07T06:51:48Z
  • dc.date.issued 2022
  • dc.description.abstract Overactivation of poly (ADPribose) polymerases (PARPs) is involved in cancer-induced cachexia. We hypothesized that the PARP inhibitor rucaparib may improve muscle mass and reduce damage in cancer cachexia mice. In mouse diaphragm and gastrocnemius (LP07 lung adenocarcinoma) treated with PARP inhibitor (rucaparib,150 mg/kg body weight/24 h for 20 days) and in non-tumor control animals, body, muscle, and tumor weights; tumor area; limb muscle strength; physical activity; muscle structural abnormalities, damage, and phenotype; PARP activity; and proteolytic and autophagy markers were quantified. In cancer cachexia mice compared to non-cachexia controls, body weight and body weight gain, muscle weight, limb strength, physical activity, and muscle fiber size significantly declined, while levels of PARP activity, plasma troponin I, muscle damage, and proteolytic and autophagy markers increased. Treatment with the PARP inhibitor rucaparib elicited a significant improvement in body weight gain, tumor size and weight, physical activity, muscle damage, troponin I, and proteolytic and autophagy levels. PARP pharmacological inhibition did not exert any significant improvements in muscle weight, fiber size, or limb muscle strength. Treatment with rucaparib, however, improved muscle damage and structural abnormalities and physical activity in cancer cachexia mice. These findings suggest that rucaparib exerts its beneficial effects on cancer cachexia performance through the restoration of muscle structure.
  • dc.description.sponsorship Project “FI19/00001” funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union. 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 CIBERES 2021 funded by Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation; Spanish Respiratory Society (SEPAR), 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, Duran X, Yélamos J, Barreiro E. Attenuation of muscle damage, structural abnormalities, and physical activity in respiratory and limb muscles following treatment with rucaparib in lung cancer cachexia mice. Cancers (Basel). 2022 Jun 11;14(12):2894. DOI: 10.3390/cancers14122894
  • dc.identifier.doi http://dx.doi.org/10.3390/cancers14122894
  • dc.identifier.issn 2072-6694
  • dc.identifier.uri http://hdl.handle.net/10230/57497
  • dc.language.iso eng
  • dc.publisher MDPI
  • dc.relation.ispartof Cancers (Basel). 2022 Jun 11;14(12):2894
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-112526RB-I00
  • dc.rights © 2022 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 PARP inhibitor rucaparib
  • dc.subject.keyword Lung-cancer-induced cachexia
  • dc.subject.keyword Muscle damage
  • dc.subject.keyword Muscle structural abnormalities
  • dc.subject.keyword Physical activity
  • dc.subject.keyword Proteolytic and autophagy markers
  • dc.subject.keyword Respiratory and limb muscles
  • dc.title Attenuation of muscle damage, structural abnormalities, and physical activity in respiratory and limb muscles following treatment with rucaparib in lung cancer cachexia mice
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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Articles (Hospital del Mar Research Institute)
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