Dietary supplementation with isoflavones prevents muscles wasting in tumor-bearing mice

Katsuya Hirasaka, Shinobu Saito, Saki Yamaguchi, Riho Miyazaki, Yao Wang, Marie Haruna, Shigeto Taniyama, Atsushi Higashitani, Junji Terao, Takeshi Nikawa, Katsuyasu Tachibana

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)

    Abstract

    Summary 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.

    Original languageEnglish
    Pages (from-to)178-184
    Number of pages7
    JournalJournal of nutritional science and vitaminology
    Volume62
    Issue number3
    DOIs
    Publication statusPublished - 2016

    Keywords

    • Isoflavone
    • Muscle wasting
    • Tumor
    • Ubiquitin ligase

    ASJC Scopus subject areas

    • Medicine (miscellaneous)
    • Nutrition and Dietetics

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