Icariside II, a natural mTOR inhibitor, disrupts aberrant energy homeostasis via suppressing mTORC1-4E-BP1 axis in sarcoma cells.
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.
['Zhang|Chao|C|', 'Yang|Lei|L|', 'Geng|Ya-di|YD|', 'An|Fa-Liang|FL|', 'Xia|Yuan-Zheng|YZ|', 'Guo|Chao|C|', 'Luo|Jian-Guang|JG|', 'Zhang|Lu-Yong|LY|', 'Guo|Qing-Long|QL|', 'Kong|Ling-Yi|LY|']
D048868:Adaptor Proteins, Signal Transducing D000818:Animals D018797:Cell Cycle Proteins D045744:Cell Line, Tumor D049109:Cell Proliferation D004365:Drugs, Chinese Herbal D034181:Epimedium D005419:Flavonoids D006019:Glycolysis D006706:Homeostasis D006801:Humans D008297:Male D051379:Mice D008813:Mice, Inbred ICR D010750:Phosphoproteins D014176:Protein Biosynthesis D016271:Proto-Oncogene Proteins c-myc D034622:RNA Interference D034741:RNA, Small Interfering D000076226:Rapamycin-Insensitive Companion of mTOR Protein D000076223:Regulatory-Associated Protein of mTOR D012509:Sarcoma D015398:Signal Transduction D058570:TOR Serine-Threonine Kinases D023041:Xenograft Model Antitumor Assays
Icariside II aberrant energy homeostasis mTORC1-4E-BP1 axis glycolysis mRNA translation