Quercetin suppresses insulin receptor signaling through inhibition of the insulin ligand–receptor binding and therefore impairs cancer cell proliferation |
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Authors: | Feng Wang Yong Yang |
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Institution: | 1. Department of Gastroenterology, The Tenth People’s Hospital of Shanghai, Tongji University, Shanghai 200072, People’s Republic of China;2. Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA;3. Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA |
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Abstract: | Although the flavonoid quercetin is known to inhibit activation of insulin receptor signaling, the inhibitory mechanism is largely unknown. In this study, we demonstrate that quercetin suppresses insulin induced dimerization of the insulin receptor (IR) through interfering with ligand–receptor interactions, which reduces the phosphorylation of IR and Akt. This inhibitory effect further inhibits insulin stimulated glucose uptake due to decreased cell membrane translocation of glucose transporter 4 (GLUT4), resulting in impaired cancer cell proliferation. The effect of quercetin in inhibiting tumor growth was also evident in an in vivo model, indicating a potential future application for quercetin in the treatment of cancers. |
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Keywords: | Quercetin Insulin receptor signaling Single-molecule imaging Single-molecule force measurement Cancer therapy |
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