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.

Dietary intake of probiotic kimchi ameliorated IL-6-driven cancer cachexia

“…First, encouraging mTOR and AKT signaling to overcome sarcopenia with adalimumab, silver linings on the horizon by Ebner & Haehling, (42) is recommended since long-term use of mTOR inhibitors led to a marked loss of muscle mass. (43) As summarized by several investigators (44)(45)(46) and ours in the current study ( Fig. 6), molecular substrates and mechanisms underlying the dysregulation of skeletal muscle synthesis and degradation included proinflammatory cytokines such as TNF-a, IL-1, IL-6 and related signaling transduction systems such as NF-kB, MAPKs, acute phase reactants, and myostatin-activin-SMAD pathways.…”

Chemotherapy‐induced cachexia dysregulates hypothalamic and systemic lipoamines and is attenuated by cannabigerol

“…A very limited number of pre‐clinical studies have attempted to investigate the pathophysiology of chemotherapy‐induced cachexia, and the efficacy of anti‐cachectic interventions, in tumour‐bearing models . However, the number of experimental groups necessitated by this approach limits the power of such designed studies to investigate the chemotherapy‐induced cachectic phenotype in detail.…”

“…A very limited number of pre-clinical studies have attempted to investigate the pathophysiology of chemotherapy-induced cachexia, and the efficacy of anticachectic interventions, in tumour-bearing models. 8,67,68 However, the number of experimental groups necessitated by this approach limits the power of such designed studies to investigate the chemotherapy-induced cachectic phenotype in detail. The present study was specifically designed to overcome such limitations, and the inherent impossibility of administering chemotherapy agents to cancer-naïve human subjects, such that it had the power to provide a comprehensive multi-omic characterization of cisplatin-induced cachexia, and assess the efficacy of CBG at multiple doses.…”

“…In addition to the well-documented side effects of anorexia and chemotherapy-induced nausea and vomiting (CINV), evidence is emerging for comorbidities that are closely related to cancer-induced cachexia, characterized by muscle atrophy and metabolic dysregulation that is qualitatively distinct from nausea and starvation-induced pathophysiology. [3][4][5][6][7][8] This syndrome, which we and others describe as chemotherapy-induced cachexia, 9 is highly debilitating to patients, has a dose-limiting effect on treatment efficacy, and compromises quality of life and ultimately mortality. Despite a considerable translational research effort and numerous clinical trials, to date no specific treatments for cancerinduced cachexia are currently licensed, 10 and strategies to ameliorate the side effects of chemotherapy are limited to anti-emetics and control of acute nausea.…”

“…While several decades of research have helped elucidate the pathophysiology of the cancer‐induced cachexia syndrome, less appreciated is the contributory role of cytotoxic chemotherapy regimens. In addition to the well‐documented side effects of anorexia and chemotherapy‐induced nausea and vomiting (CINV), evidence is emerging for comorbidities that are closely related to cancer‐induced cachexia, characterized by muscle atrophy and metabolic dysregulation that is qualitatively distinct from nausea and starvation‐induced pathophysiology . This syndrome, which we and others describe as chemotherapy‐induced cachexia, is highly debilitating to patients, has a dose‐limiting effect on treatment efficacy, and compromises quality of life and ultimately mortality.…”