title: Supplementation of Magnolol Attenuates Skeletal Muscle Atrophy in Bladder Cancer-Bearing Mice Undergoing Chemotherapy via Suppression of FoxO3 Activation and Induction of IGF-1.
abstract: Skeletal muscle atrophy, the most prominent phenotypic feature of cancer cachexia, is often observed in cancer patients undergoing chemotherapy. Magnolol (M) extracted from Magnolia officinalis exhibits several pharmacological effects including anti-inflammatory and anticancer activities. In this study, we investigated whether magnolol supplementation protects against the development of cachexia symptoms in bladder cancer-bearing mice undergoing chemotherapy. Combined treatment of magnolol with chemotherapeutic drugs, such as gemcitabine and cisplatin (TGCM) or gemcitabine (TGM), markedly attenuates the body weight loss and skeletal muscle atrophy compared with conventional chemotherapy (TGC). The antiatrophic effect of magnolol may be associated with inhibition of myostatin and activin A formation, as well as FoxO3 transcriptional activity resulting from Akt activation, thereby suppressing ubiquitin ligases MuRF-1 and MAFbx/atrogin-1 expression, as well as proteasomal enzyme activity. Notably, magnolol-induced insulin-like growth factor 1 (IGF-1) production and related protein synthesis may also contribute to its protective effects. The decreased food intake, and intestinal injury and dysfunction observed in the mice of TGC group were significantly improved in the TGCM and TGM groups. Moreover, the increased inflammatory responses evidenced by elevation of proinflammatory cytokine formation and NF-κB activation occurred in the atrophying muscle of TGC group were markedly inhibited in mice of combined treatment with magnolol. In summary, these findings support that magnolol is a promising chemopreventive supplement for preventing chemotherapy-induced skeletal muscle atrophy associated with cancer cachexia by suppressing muscle protein degradation, and inflammatory responses, as well as increasing IGF-1-mediated protein synthesis.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Meng-Chuan
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Department of Pathology, Cardinal Tien Hospital; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Yen-Lin
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Division of Biopharmaceuticals, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chi-Feng
authors.initials: CF
authors.lastname: Lee
authors.affiliation: Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
authors.forename: Chih-Huang
authors.initials: CH
authors.lastname: Hung
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.|Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.|Department of Biotechnology, Asia University, Taichung, Taiwan.|China Medical University Hospital, China Medical University, Taichung, Taiwan.
authors.forename: Tz-Chong
authors.initials: TC
authors.lastname: Chou
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D017705:Lignans / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009133:Muscular Atrophy / Q000188:drug therapy*; D016328:NF-kappa B / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D001713:Biphenyl Compounds; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D015850:Interleukin-6; D017705:Lignans; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C005498:magnolol; D007334:Insulin-Like Growth Factor I; D046988:Proteasome Endopeptidase Complex