Combined administration of fucoidan ameliorates tumor and chemotherapy-induced skeletal muscle atrophy in bladder cancer-bearing mice

// Meng-Chuan Chen 1, * , Wen-Lin Hsu 2, 3, * , Pa-An Hwang 4 , Yen-Lin Chen 5 , Tz-Chong Chou 6, 7, 8 1 Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan 2 School of Medicine, Tzu Chi University, Hualien, Taiwan 3 Department of Radiation Oncology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan 4 Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan 5 Department of Pathology, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan 6 Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan 7 Department of Biotechnology, Asia University, Taichung, Taiwan 8 China Medical University Hospital, China Medical University, Taichung, Taiwan * These authors have contributed equally to this work Correspondence to: Tz-Chong Chou, email: tcchou48@mail.tcu.edu.tw Keywords: fucoidan, cancer cachexia, muscle atrophy, chemotherapy, inflammation Received: November 11, 2015 Accepted: May 17, 2016 Published: June 13, 2016 ABSTRACT 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.