Quercetin Improved Muscle Mass And Mitochondrial Content With Cancer And Chemotherapy-induced Cachexia

PURPOSE: Cachexia or the unintentional loss of body weight with chronic disease is associated with a doubling in hospital stay and increased healthcare cost for cancer patients. A substantial percent of cancer patients diagnosed with cachexia do not survive treatment. Therefore, investigating potential anti-cachectic compounds should consider the use of preclinical models involving malignancies in conjunction with its treatments. Quercetin an organic polyphenolic flavonoid commonly found in fruits and vegetables has demonstrated anti-inflammatory and antioxidant properties with promise in protecting against cachexia. While quercetin has been shown to mitigate cancer-induced wasting and chemotherapy-induced fatigue, whether quercetin is efficacious in maintaining muscle mass in a tumor bearing animal receiving chemotherapy has not been investigated. METHODS: Male CD2F1 mice bearing C26 tumors were given intraperitoneal injection of fluorouracil (5FU; 30 mg/kg of lean mass i.p.) concomitant with quercetin (Quer; 50 mg/kg of body weight via oral gavage) or vehicle. RESULTS: Both C26 + 5FU and C26 + 5FU + Quer had similar body weight loss (-14.5% vs -13.8%; p = 0.5); however, muscle mass and muscle cross sectional area (CSA) was greater in C26 + 5FU + Quer compared to C26 + 5FU (2327μm2 vs 1763μm2; p < 0.05). Mice in the C26 + 5FU + Quer group showed greater CSA of both glycolytic and oxidative fibers. Additionally, C26 + 5FU + Quer had a greater number (30.2 vs 19.5; p < 0.05) and larger (79149nm2 vs 53476nm2; p < 0.05) intermyofibrillar mitochondria with increased relative protein expression of mitochondrial complexes V, III, and II as well as cytochrome c expression. C26 + 5FU + Quer also had increased MFN1 and reduced FIS1 relative protein expression without apparent benefits to muscle inflammatory signaling. CONCLUSIONS: Our data suggest that quercetin protected against cancer and chemotherapy-induced muscle mass loss through improved mitochondrial homeostatic balance.