Oncotarget

Research Papers:

Icariside II, a natural mTOR inhibitor, disrupts aberrant energy homeostasis via suppressing mTORC1-4E-BP1 axis in sarcoma cells

Chao Zhang _, Lei Yang, Ya-di Geng, Fa-liang An, Yuan-zheng Xia, Chao Guo, Jian-guang Luo, Lu-yong Zhang, Qing-long Guo and Ling-yi Kong

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Oncotarget. 2016; 7:27819-27837. https://doi.org/10.18632/oncotarget.8538

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Abstract

Chao Zhang1, Lei Yang1, Ya-di Geng1, Fa-liang An1, Yuan-zheng Xia1, Chao Guo1, Jian-guang Luo1, Lu-yong Zhang1, Qing-long Guo1, Ling-yi Kong1

1State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, China

Correspondence to:

Ling-yi Kong, e-mail: [email protected]

Keywords: Icariside II, aberrant energy homeostasis, glycolysis, mRNA translation, mTORC1-4E-BP1 axis

Received: July 20, 2015    Accepted: March 23, 2016    Published: April 1, 2016

ABSTRACT

The aberrant energy homeostasis that characterized by high rate of energy production (glycolysis) and energy consumption (mRNA translation) is associated with the development of cancer. As mammalian target of rapamycin (mTOR) is a critical regulator of aberrant energy homeostasis, it is an attractive target for anti-tumor intervention. The flavonoid compound Icariside II (IS) is a natural mTOR inhibitor derived from Epimedium. Koreanum. Herein, we evaluate the effect of IS on aberrant energy homeostasis. The reduction of glycolysis and mRNA translation in U2OS (osteosarcoma), S180 (fibrosarcoma) and SW1535 (chondrosarcoma) cells observed in our study, indicate that, IS inhibits aberrant energy homeostasis. This inhibition is found to be due to suppression of mammalian target of rapamycin complex 1 (mTORC1)-eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) axis through blocking the assembly of mTORC1. Furthermore, IS inhibits the cap-dependent translation of c-myc through mTORC1-4E-BP1 axis which links the relationship between mRNA translation and glycolysis. Inhibition of aberrant energy homeostasis by IS, contributes to its in vitro and in vivo anti-proliferation activity. These data indicate that IS disrupts aberrant energy homeostasis of sarcoma cells through suppression of mTORC1-4E-BP1 axis, providing a novel mechanism of IS to inhibit cell proliferation in sarcoma cells.


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