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

Pérez-Peiró, Maria; Duran Jordà, Xavier, 1974-; Yélamos López, José; Barreiro Portela, Esther

doi:http://dx.doi.org/10.3390/cancers14122894

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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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

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.