{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T17:48:04Z","timestamp":1781200084180,"version":"3.54.1"},"reference-count":43,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T00:00:00Z","timestamp":1628812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS 18\/00075 (FEDER)"],"award-info":[{"award-number":["FIS 18\/00075 (FEDER)"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007509","name":"Sociedad Espa\u00f1ola de Neumolog\u00eda y Cirug\u00eda Tor\u00e1cica","doi-asserted-by":"publisher","award":["SEPAR 2020"],"award-info":[{"award-number":["SEPAR 2020"]}],"id":[{"id":"10.13039\/501100007509","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Muscle wasting and cachexia are prominent comorbidities in cancer. Treatment with polyphenolic compounds may partly revert muscle wasting. We hypothesized that treatment with curcumin or resveratrol in cancer cachectic mice may improve muscle phenotype and total body weight through attenuation of several proteolytic and signaling mechanisms in limb muscles. In gastrocnemius and soleus muscles of cancer cachectic mice (LP07 adenocarcinoma cells, N = 10\/group): (1) LC-induced cachexia, (2) LC-cachexia+curcumin, and (3) LC-cachexia + resveratrol, muscle structure and damage (including blood troponin I), sirtuin-1, proteolytic markers, and signaling pathways (NF-\u03baB and FoxO3) were explored (immunohistochemistry and immunoblotting). Compared to nontreated cachectic mice, in LC-cachexia + curcumin and LC-cachexia + resveratrol groups, body and muscle weights (gastrocnemius), limb muscle strength, muscle damage, and myofiber cross-sectional area improved, and in both muscles, sirtuin-1 increased, while proteolysis (troponin I), proteolytic markers, and signaling pathways were attenuated. Curcumin and resveratrol elicited beneficial effects on fast- and slow-twitch limb muscle phenotypes in cachectic mice through sirtuin-1 activation, attenuation of atrophy signaling pathways, and proteolysis in cancer cachectic mice. These findings have future therapeutic implications as these natural compounds, separately or in combination, may be used in clinical settings of muscle mass loss and dysfunction including cancer cachexia.<\/jats:p>","DOI":"10.3390\/molecules26164904","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T09:22:38Z","timestamp":1628846558000},"page":"4904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Curcumin and Resveratrol Improve Muscle Function and Structure through Attenuation of Proteolytic Markers in Experimental Cancer-Induced Cachexia"],"prefix":"10.3390","volume":"26","author":[{"given":"Antonio","family":"Penedo-V\u00e1zquez","sequence":"first","affiliation":[{"name":"Department-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, IMIM-Hospital del Mar, Parc de Salut Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Duran","sequence":"additional","affiliation":[{"name":"Scientific and Technical Department, Hospital del Mar-IMIM, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Mateu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hospital del Mar, Parc de Salut Mar, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7175-8789","authenticated-orcid":false,"given":"Adri\u00e1n","family":"L\u00f3pez-Postigo","sequence":"additional","affiliation":[{"name":"Department-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, IMIM-Hospital del Mar, Parc de Salut Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Barreiro","sequence":"additional","affiliation":[{"name":"Department-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, IMIM-Hospital del Mar, Parc de Salut Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), 08003 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1097\/CCO.0000000000000517","article-title":"Cancer cachexia, a clinical challenge","volume":"31","author":"Busquets","year":"2019","journal-title":"Curr. Opin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1164\/rccm.201412-2189OE","article-title":"Muscle dysfunction in patients with lung diseases a growing epidemic","volume":"191","author":"Barreiro","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1002\/jcp.24611","article-title":"Pharmacological Strategies in Lung Cancer-Induced Cachexia: Effects on Muscle Proteolysis, Autophagy, Structure, and Weakness","volume":"229","author":"Fermoselle","year":"2014","journal-title":"J. Cell. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1186\/s12967-016-1003-9","article-title":"Phenotypic and metabolic features of mouse diaphragm and gastrocnemius muscles in chronic lung carcinogenesis: Influence of underlying emphysema","volume":"14","author":"Blanco","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.biochi.2018.04.009","article-title":"Effects of the beta 2 agonist formoterol on atrophy signaling, autophagy, and muscle phenotype in respiratory and limb muscles of rats with cancer-induced cachexia","volume":"149","author":"Busquets","year":"2018","journal-title":"Biochimie"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e4109","DOI":"10.7717\/peerj.4109","article-title":"Formoterol attenuates increased oxidative stress and myosin protein loss in respiratory and limb muscles of cancer cachectic rats","volume":"5","author":"Busquets","year":"2017","journal-title":"PeerJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"18041","DOI":"10.1002\/jcp.28437","article-title":"Reduced lung cancer burden by selective immunomodulators elicits improvements in muscle proteolysis and strength in cachectic mice","volume":"234","author":"Tang","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.freeradbiomed.2014.11.006","article-title":"Oxidative stress, redox signaling pathways, and autophagy in cachectic muscles of male patients with advanced COPD and lung cancer","volume":"79","author":"Rodriguez","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.bcp.2018.07.050","article-title":"Commentary Polyphenols, food and pharma. Current knowledge and directions for future research","volume":"156","author":"Moreno","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_10","first-page":"1267","article-title":"Curcumin protects against myocardial infarction-induced cardiac fibrosis via SIRT1 activation in vivo and in vitro","volume":"10","author":"Xiao","year":"2016","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s00395-012-0263-7","article-title":"The effects of curcumin post-treatment against myocardial ischemia and reperfusion by activation of the JAK2\/STAT3 signaling pathway","volume":"107","author":"Duan","year":"2012","journal-title":"Basic Res. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Receno, C.N., Liang, C., Korol, D.L., Atalay, M., Heffernan, K.S., Brutsaert, T.D., and Deruisseau, K.C. (2019). Effects of prolonged dietary curcumin exposure on skeletal muscle biochemical and functional responses of aged male rats. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051178"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4678","DOI":"10.3892\/mmr.2015.3322","article-title":"Curcumin inhibits autophagy and apoptosis in hypoxia\/reoxygenation-induced myocytes","volume":"11","author":"Huang","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Thaloor, D., Miller, K.J., Gephart, J., Mitchell, P.O., and Pavlath, G.K. (1999). Systemic administration of the NF-\u03baB inhibitor curcumin stimulates muscle regeneration after traumatic injury. Am. J. Physiol. Cell Physiol., 277.","DOI":"10.1152\/ajpcell.1999.277.2.C320"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ma\u00f1as-Garc\u00eda, L., Guitart, M., Duran, X., and Barreiro, E. (2020). Satellite cells and markers of muscle regeneration during unloading and reloading: Effects of treatment with resveratrol and curcumin. Nutrients, 12.","DOI":"10.3390\/nu12061870"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0304-3835(01)00456-6","article-title":"Curcumin, a natural product present in turmeric, decreases tumor growth but does not behave as an anticachectic compound in a rat model","volume":"167","author":"Busquets","year":"2001","journal-title":"Cancer Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R1572","DOI":"10.1152\/ajpregu.00489.2010","article-title":"Mediation of endogenous antioxidant enzymes and apoptotic signaling by resveratrol following muscle disuse in the gastrocnemius muscles of young and old rats","volume":"299","author":"Jackson","year":"2010","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chaplin, A., Carp\u00e9n\u00e9, C., and Mercader, J. (2018). Resveratrol, Metabolic Syndrome, and Gut Microbiota. Nutrients, 10.","DOI":"10.3390\/nu10111651"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"L774","DOI":"10.1152\/ajplung.00110.2004","article-title":"Anti-inflammatory effects of resveratrol in lung epithelial cells: Molecular mechanisms","volume":"287","author":"Donnelly","year":"2004","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1743-7075-11-35","article-title":"Effects and mechanisms of resveratrol on the amelioration of oxidative stress and hepatic steatosis in KKAy mice","volume":"11","author":"Zhu","year":"2014","journal-title":"Nutr. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1039\/C8FO02518E","article-title":"Resveratrol regulates skeletal muscle fibers switching through the AdipoR1-AMPK-PGC-1\u03b1 pathway","volume":"10","author":"Jiang","year":"2019","journal-title":"Food Funct."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6968","DOI":"10.1074\/jbc.M112.431155","article-title":"Sirtuin 1-mediated effects of exercise and resveratrol on mitochondrial biogenesis","volume":"288","author":"Menzies","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.femsyr.2004.06.015","article-title":"A novel assay for replicative lifespan in Saccharomyces cerevisiae","volume":"5","author":"Jarolim","year":"2004","journal-title":"FEMS Yeast Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.12659\/MSM.913409","article-title":"Therapeutic Effects of Resveratrol Liposome on Muscle Injury in Rats","volume":"25","author":"Feng","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.clnu.2006.12.001","article-title":"Resveratrol does not ameliorate muscle wasting in different types of cancer cachexia models","volume":"26","author":"Busquets","year":"2007","journal-title":"Clin. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1017\/S0007114507798938","article-title":"Biomarkers of the intake of dietary polyphenols: Strengths, limitations and application in nutrition research","volume":"99","author":"Spencer","year":"2008","journal-title":"Br. J. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ma\u00f1as-garc\u00eda, L., Bargall\u00f3, N., Gea, J., and Barreiro, E. (2020). Muscle phenotype, proteolysis, and atrophy signaling during reloading in mice: Effects of curcumin on the gastrocnemius. Nutrients, 12.","DOI":"10.3390\/nu12020388"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ma\u00f1as-Garc\u00eda, L., Penedo-V\u00e1zquez, A., L\u00f3pez-Postigo, A., Deschrevel, J., Dur\u00e1n, X., and Barreiro, E. (2020). Prolonged immobilization exacerbates the loss of muscle mass and function induced by cancer-associated cachexia through enhanced proteolysis in mice. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218167"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1016\/j.bbagen.2015.09.020","article-title":"MicroRNA expression and protein acetylation pattern in respiratory and limb muscles of Parp-1-\/- and Parp-2-\/- mice with lung cancer cachexia","volume":"1850","author":"Fermoselle","year":"2015","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_30","first-page":"639","article-title":"Vidal, M.; Puricelli, L.I.; Klein, S.M.; De Kier Joffe, E.D. New murine cell line derived from a spontaneous lung tumor induces paraneoplastic syndromes","volume":"18","author":"Urtreger","year":"2001","journal-title":"Int. J. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3744","DOI":"10.1002\/jcp.25851","article-title":"Role of PARP activity in lung cancer-induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype","volume":"232","author":"Langohr","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"430","DOI":"10.18632\/aging.100312","article-title":"The physiological roles of Sirt1 in skeletal muscle","volume":"3","author":"Pardo","year":"2011","journal-title":"Aging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.stem.2014.12.004","article-title":"The NAD+-dependent sirt1 deacetylase translates a metabolic switch into regulatory epigenetics in skeletal muscle stem cells","volume":"16","author":"Ryall","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1152\/japplphysiol.00798.2017","article-title":"The phosphodiesterase-4 inhibitor roflumilast reverts proteolysis in skeletal muscle cells of patients with COPD cachexia","volume":"125","author":"Barreiro","year":"2018","journal-title":"J. Appl. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.2147\/CIA.S223805","article-title":"Recovery of Bone and Muscle Mass in Patients with Chronic Kidney Disease and Iron Overload on Hemodialysis and Taking Combined Supplementation with Curcumin and Resveratrol","volume":"14","year":"2019","journal-title":"Clin. Interv. Aging"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1002\/cncr.29793","article-title":"Resveratrol inhibits ovarian tumor growth in an in vivo mouse model","volume":"122","author":"Tan","year":"2016","journal-title":"Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e10","DOI":"10.1038\/cddis.2009.8","article-title":"Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy","volume":"1","author":"Morselli","year":"2010","journal-title":"Cell Death Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1093\/gerona\/glx089","article-title":"Resveratrol Enhances Exercise-Induced Cellular and Functional Adaptations of Skeletal Muscle in Older Men and Women","volume":"72","author":"Alway","year":"2017","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/acel.12342","article-title":"Longevity and skeletal muscle mass: The role of IGF signalling, the sirtuins, dietary restriction and protein intake","volume":"14","author":"Sharples","year":"2015","journal-title":"Aging Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1007\/s11357-020-00295-w","article-title":"Towards resolving the enigma of the dichotomy of resveratrol: Cis- and trans-resveratrol have opposite effects on TyrRS-regulated PARP1 activation","volume":"43","author":"Jhanji","year":"2021","journal-title":"GeroScience"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nature14028","article-title":"A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol","volume":"519","author":"Sajish","year":"2015","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1800715","DOI":"10.1002\/mnfr.201800715","article-title":"Endothelial Cells Deconjugate Resveratrol Metabolites to Free Resveratrol: A Possible Role in Tissue Factor Modulation","volume":"63","author":"Motilva","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10219","DOI":"10.1038\/s41598-019-46678-8","article-title":"Nicotinamide Augments the Anti-Inflammatory Properties of Resveratrol through PARP1 Activation","volume":"9","author":"Yanez","year":"2019","journal-title":"Sci. Rep."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/16\/4904\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:45:26Z","timestamp":1760165126000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/16\/4904"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,13]]},"references-count":43,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["molecules26164904"],"URL":"https:\/\/doi.org\/10.3390\/molecules26164904","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,13]]}}}