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Magnolol inhibits myotube atrophy induced by cancer cachexia through myostatin signaling pathway in vitro

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Abstract

Cancer cachexia is a complex and multifactorial syndrome that influences about 50–80% of cancer patients and may lead to 20% of cancer deaths and muscle atrophy is the key characteristic of the syndrome. Recent researches have shown that myostatin is a negative regulator in the growth and differentiation of skeletal muscle. Herein, C2C12 cancer cachexia model was established with C26 conditioned culture medium (CCM), then treated with magnolol to evaluate the pharmacological activity of magnolol in myotube atrophy. Our results demonstrated that magnolol inhibited the activity of myostatin promotor and the myostatin signaling pathway. In C2C12 cancer cachexia model, magnolol decreased myostatin expression, inhibited the phosphorylation of SMAD2/3 activated by C26 conditioned culture medium (CCM), and elevated the phosphorylation of FOXO3a lowered by CCM. Myosin heavy chain (MyHC), myogenin (MyoG), and myogenic differentiation (MyoD), as three common myotube markers in C2C12 myotube, were decreased by CCM, which could be effectively reversed by magnolol via activation of AKT/mTOR-regulated protein synthesis and inhibition of ubiquitin-mediated proteolysis. This study reveals that magnolol inhibits myotube atrophy induced by CCM by increasing protein synthesis and decreasing ubiquitin-mediated proteolysis, so that magnolol is a promising leading compound in treating muscle atrophy induced by cancer cachexia.

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Acknowledgments

This work was supported by grants from CAMS Innovation Fund for Medical Sciences (CIFMS, 2016-I2M-02-002) and “Significant New Drug Development” Major Science and Technology Development Projects of China (No.2018ZX09711001-007-002).

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Authors and Affiliations

  1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 1# Tiantan Xili, Dongcheng District, Beijing, 100050, China

    Zhijuan Ge, Dong Liu, Yue Shang, Yi Li & Shu-zhen Chen

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  1. Zhijuan Ge
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  2. Dong Liu
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Correspondence to Shu-zhen Chen.

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Ge, Z., Liu, D., Shang, Y. et al. Magnolol inhibits myotube atrophy induced by cancer cachexia through myostatin signaling pathway in vitro. J Nat Med 74, 741–749 (2020). https://doi.org/10.1007/s11418-020-01428-3

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  • DOI: https://doi.org/10.1007/s11418-020-01428-3

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