title: Oral resveratrol therapy inhibits cancer-induced skeletal muscle and cardiac atrophy in vivo.
abstract: The mechanism by which cancer mediates muscle atrophy has been delineated in the past 3 decades and includes a prominent role of tumor-derived cytokines, such as IL-6, TNFα, and IL-1. These cytokines interact with their cognate receptors on muscle to activate the downstream transcription factor NF-κB and induce sarcomere proteolysis. Experimentally, inhibiting NF-κB signaling largely prevents cancer-induced muscle wasting, indicating its prominent role in muscle atrophy. Resveratrol, a natural phytoalexin found in the skin of grapes, has recently been shown to inhibit NF-κB in cancer cells, which led us to hypothesize that it might have a protective role in cancer cachexia. Therefore, we investigated whether daily oral resveratrol could protect against skeletal muscle loss and cardiac atrophy in an established mouse model. We demonstrate resveratrol inhibits skeletal muscle and cardiac atrophy induced by C26 adenocarcinoma tumors through its inhibition of NF-κB (p65) activity in skeletal muscle and heart. These studies demonstrate for the first time the utility of oral resveratrol therapy to provide clinical benefit in cancer-induced atrophy through the inhibition of NF-κB in muscle. These findings may have application in the treatment of diseases with parallel pathophysiologies such as muscular dystrophy and heart failure.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Shadfar
authors.forename: Marion E
authors.initials: ME
authors.lastname: Couch
authors.forename: Kibwei A
authors.initials: KA
authors.lastname: McKinney
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Weinstein
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Yin
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Rodríguez
authors.forename: Denis C
authors.initials: DC
authors.lastname: Guttridge
authors.forename: Monte
authors.initials: M
authors.lastname: Willis
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000503:physiopathology*; D000284:Administration, Oral; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D002100:Cachexia / Q000517:prevention & control; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000209:etiology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D051996:Transcription Factor RelA / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
chemical_list: D009124:Muscle Proteins; D012333:RNA, Messenger; C498144:Rela protein, mouse; D013267:Stilbenes; D051996:Transcription Factor RelA; D000070584:Tripartite Motif Proteins; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; D000077185:Resveratrol