title: Antioxidant supplementation accelerates cachexia development by promoting tumor growth in C26 tumor-bearing mice.
abstract: More than 50% of patients with advanced stages of colon cancer suffer from progressive loss of skeletal muscle, called cachexia, resulting in reduced quality of life and shortened survival. It is becoming evident that reactive oxygen species (ROS) regulate pathways controlling skeletal muscle atrophy. Herein we tested the hypothesis that antioxidant supplementation could prevent skeletal muscle atrophy in a model of cachectic Colon 26 (C26) tumor-bearing mice. Seven-week-old BALB/c mice were subcutaneously inoculated with colon 26 (C26) cancer cells or PBS. Then C26-mice were daily gavaged during 22 days either with PBS (vehicle) or an antioxidant cocktail whose composition is close to that of commercial dietary antioxidant supplements (rich in catechins, quercetin and vitamin C). We found that antioxidants enhanced weight loss and caused premature death of mice. Antioxidants supplementation failed to prevent (i) the increase in plasma TNF-α levels and systemic oxidative damage, (ii) skeletal muscle atrophy and (iii) activation of the ubiquitin-proteasome system (MuRF-1, MAFbx and polyubiquitinated proteins). Accordingly, immunohistological staining for Ki-67 and the expression of cell cycle inhibitors demonstrated that tumor of supplemented mice developed faster with a concomitant decrease in oxidative damage. Previous studies have shown that the use of catechins and quercetin separately can improve the musculoskeletal function in cachectic animals. However, our results indicate that the combination of these antioxidants reduced survival and enhanced cachexia in C26-mice.
authors.affiliation: EA1274 Laboratory "Movement, Sport and Health Sciences" M2S, University of Rennes 2-ENS Rennes, Bruz, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Assi
authors.affiliation: EA1274 Laboratory "Movement, Sport and Health Sciences" M2S, University of Rennes 2-ENS Rennes, Bruz, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Derbré
authors.affiliation: EA1274 Laboratory "Movement, Sport and Health Sciences" M2S, University of Rennes 2-ENS Rennes, Bruz, France.
authors.forename: Luz
authors.initials: L
authors.lastname: Lefeuvre-Orfila
authors.affiliation: EA1274 Laboratory "Movement, Sport and Health Sciences" M2S, University of Rennes 2-ENS Rennes, Bruz, France. Electronic address: amelie.rebillard@univ-rennes2.fr.
authors.forename: Amélie
authors.initials: A
authors.lastname: Rébillard
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects*; D002100:Cachexia / Q000139:chemically induced*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000150:complications* / Q000473:pathology; D019587:Dietary Supplements; D004789:Enzyme Activation; D015227:Lipid Peroxidation; D008297:Male; D008807:Mice, Inbred BALB C; D009133:Muscular Atrophy / Q000139:chemically induced; D009368:Neoplasm Transplantation; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D054875:Ubiquitination
chemical_list: D000975:Antioxidants; D051057:Proto-Oncogene Proteins c-akt; D046988:Proteasome Endopeptidase Complex
keywords: Muscle wasting; Myostatin; Oxidative stress; TNF-α; Tumor growth