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

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.

• Authors: Meng-Chuan Chen, Wen-Lin Hsu, Pa-An Hwang, Yen-Lin Chen, Tz-Chong Chou
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 32 Pg. 51608-51618 (08 09 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27323407 (Publication Type: Journal Article)

Chemical References

• Polysaccharides
• fucoidan

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Cachexia (chemically induced, drug therapy)
• Carcinoma, Transitional Cell (drug therapy, pathology)
• Cell Line, Tumor
• Drug Therapy, Combination
• Female
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Muscle, Skeletal (drug effects, pathology)
• Muscular Atrophy (chemically induced, drug therapy)
• Polysaccharides (administration & dosage)
• Urinary Bladder Neoplasms (drug therapy, pathology)
• Xenograft Model Antitumor Assays