title: Dietary Supplementation with Isoflavones Prevents Muscle Wasting in Tumor-Bearing Mice.
abstract: Proinflammatory cytokines contribute to the progression of muscle wasting caused by ubiquitin-proteasome-dependent proteolysis. We have previously demonstrated that isoflavones, such as genistein and daidzein, prevent TNF-α-induced muscle atrophy in C2C12 myotubes. In this study, we examined the effect of dietary flavonoids on the wasting of muscle. Mice were divided into the following four groups: vehicle-injected (control) mice fed the normal diet (CN); tumor-bearing mice fed the normal diet (TN); control mice fed the isoflavone diet (CI); and tumor-bearing mice fed the isoflavone diet (TI). There were no significant differences in the intake of food or body weight gain among these four groups. The wet weight and myofiber size of gastrocnemius muscle in TN significantly decreased, compared with those in CN. Interestingly, the wet weight and myofiber size of gastrocnemius muscle in TI were nearly the same as those in CN and CI, although isoflavone supplementation did not affect the increased tumor mass or concentrations of proinflammatory cytokines, such as TNF-α and IL-6, in the blood. Moreover, increased expression of muscle-specific ubiquitin ligase genes encoding MAFbx/Atrogin-1 and MuRF1 in the skeletal muscle of TN was significantly inhibited by the supplementation of isoflavones. In parallel with the expression of muscle-specific ubiquitin ligases, dietary isoflavones significantly suppressed phosphorylation of ERK in tumor-bearing mice. These results suggest that dietary isoflavones improve muscle wasting in tumor-bearing mice via the ERK signaling pathway mediated-suppression of ubiquitin ligases in muscle cells.
authors.affiliation: Graduate School of Fisheries and Environmental Sciences, Nagasaki University.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Hirasaka
authors.forename: Shinobu
authors.initials: S
authors.lastname: Saito
authors.forename: Saki
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Riho
authors.initials: R
authors.lastname: Miyazaki
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Marie
authors.initials: M
authors.lastname: Haruna
authors.forename: Shigeto
authors.initials: S
authors.lastname: Taniyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Higashitani
authors.forename: Junji
authors.initials: J
authors.lastname: Terao
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nikawa
authors.forename: Katsuyasu
authors.initials: K
authors.lastname: Tachibana
mesh_terms: D000818:Animals; D019587:Dietary Supplements; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood; D007529:Isoflavones / Q000008:administration & dosage*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology; D009133:Muscular Atrophy / Q000517:prevention & control; D009369:Neoplasms / Q000150:complications*; D009929:Organ Size; D010766:Phosphorylation; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D019282:Wasting Syndrome / Q000209:etiology / Q000517:prevention & control*
chemical_list: D015850:Interleukin-6; D007529:Isoflavones; D014409:Tumor Necrosis Factor-alpha; D044767:Ubiquitin-Protein Ligases; D048049:Extracellular Signal-Regulated MAP Kinases