Combined administration of fucoidan ameliorates tumor and chemotherapy-induced skeletal muscle atrophy in bladder cancer-bearing mice.
Cancer cachexia is characterized by anorexia, skeletal muscle atrophy, and systemic inflammation. Fucoidan extracted from brown algae exhibits anti-inflammatory and anticancer activities. However, whether fucoidan ameliorates tumour and chemotherapy-induced muscle atrophy and -related cachectic symptoms remains unknown. Compared with mice with bladder cancer treated with chemotherapy alone (TGC group), those treated with a combination of low molecular weight fucoidan (LMWF) and chemotherapy drugs such as gemcitabine and cisplatin (TGCF) showed a significant reduction of body weight loss, muscle atrophy, and intestinal injury and dysfunction. Moreover, myostatin, activin A, and pro-inflammatory cytokine production, FoxO3 expression and activation, NF-κB activation, MuRF-1 and MAFbx/atrogin-1 expression, and proteasome activity in muscle were significantly decreased in the TGCF group compared with the TGC group. In addition, insulin-like growth factor 1 (IGF-1) expression and formation, and IGF-1-regulated mTOR/p70S6k/4EBP-1 protein synthesis signalling were elevated in the TGCF group compared with the TGC group. Taken together, these results suggest that LMWF is a potential agent for preventing cancer cachexia-associated muscle atrophy during chemotherapy. Furthermore, the beneficial effect of LMWF may be attributed to suppressing NF-κB-evoked inflammation, myostatin and activin A production, and subsequent muscle proteolysis, and enhancing IGF-1-dependent protein synthesis.
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Meng-Chuan
MC
Chen
School of Medicine, Tzu Chi University, Hualien, Taiwan.|Department of Radiation Oncology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
Wen-Lin
WL
Hsu
Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan.
Pa-An
PA
Hwang
Department of Pathology, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
Yen-Lin
YL
Chen
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.
Tz-Chong
TC
Chou
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002100:Cachexia / Q000139:chemically induced / Q000188:drug therapy*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009133:Muscular Atrophy / Q000139:chemically induced / Q000188:drug therapy*; D011134:Polysaccharides / Q000008:administration & dosage*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D011134:Polysaccharides; C007789:fucoidan
cancer cachexia; chemotherapy; fucoidan; inflammation; muscle atrophy