Open Access

Matrine improves skeletal muscle atrophy by inhibiting E3 ubiquitin ligases and activating the Akt/mTOR/FoxO3α signaling pathway in C2C12 myotubes and mice

  • Authors:
    • Li Chen
    • Linlin Chen
    • Lili Wan
    • Yan Huo
    • Jinlu Huang
    • Jie Li
    • Jin Lu
    • Bo Xin
    • Quanjun Yang
    • Cheng Guo
  • View Affiliations

  • Published online on: June 19, 2019     https://doi.org/10.3892/or.2019.7205
  • Pages: 479-494
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Skeletal muscle wasting is a feature of cancer cachexia that increases patient morbidity and mortality. Matrine, the main bioactive component of Sophora flavescens, has been approved for the prevention and therapy of cancer cachexia in China. However, to the best of our knowledge, its mechanism in improving muscle wasting remains unknown. The present study demonstrated that matrine increases muscle fiber size and muscle mass in an in vivo CT26 colon adenocarcinoma cachexia mouse model. Concurrently, other cachexia symptoms, including body and organ weight loss, were alleviated. In in vitro experiments, matrine substantially improved C2C12 myoblast differentiation with or without dexamethasone treatment. In addition, matrine reduced C2C12 myotube atrophy and apoptosis induced by dexamethasone, tumor necrosis factor α and conditioned medium. Two E3 ubiquitin ligases, muscle RING‑finger containing protein‑1 and muscle atrophy F­box protein, which are specifically expressed in wasting skeletal muscle, were also significantly downregulated (P<0.05) by matrine both in C2C12 myotubes and skeletal muscle. Furthermore, matrine increased the phosphorylation of Akt, mTOR and FoxO3α in the atrophying C2C12 myotube induced by dexamethasone. In conclusion, matrine can alleviate muscle atrophy and improve myoblast differentiation possibly by inhibiting E3 ubiquitin ligases and activating the Akt/mTOR/FoxO3α signaling pathway.

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Copy and paste a formatted citation
APA
Chen, L., Chen, L., Wan, L., Huo, Y., Huang, J., Li, J. ... Guo, C. (2019). Matrine improves skeletal muscle atrophy by inhibiting E3 ubiquitin ligases and activating the Akt/mTOR/FoxO3α signaling pathway in C2C12 myotubes and mice . Oncology Reports, 42, 479-494. https://doi.org/10.3892/or.2019.7205
MLA
Chen, L., Chen, L., Wan, L., Huo, Y., Huang, J., Li, J., Lu, J., Xin, B., Yang, Q., Guo, C."Matrine improves skeletal muscle atrophy by inhibiting E3 ubiquitin ligases and activating the Akt/mTOR/FoxO3α signaling pathway in C2C12 myotubes and mice ". Oncology Reports 42.2 (2019): 479-494.
Chicago
Chen, L., Chen, L., Wan, L., Huo, Y., Huang, J., Li, J., Lu, J., Xin, B., Yang, Q., Guo, C."Matrine improves skeletal muscle atrophy by inhibiting E3 ubiquitin ligases and activating the Akt/mTOR/FoxO3α signaling pathway in C2C12 myotubes and mice ". Oncology Reports 42, no. 2 (2019): 479-494. https://doi.org/10.3892/or.2019.7205