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Quercetin Inhibits the Proliferation of Glycolysis-Addicted HCC Cells by Reducing Hexokinase 2 and Akt-mTOR Pathway

Increased glycolysis in tumor cells is associated with increased risk of tumor progression and mortality. Therefore, disruption of glycolysis, one of the main sources of cellular energy supply, can serve as a target for suppressing tumor growth and progression. Of note, hexokinase-2 (HK2) plays vita...

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Autores principales: Wu, Hongyan, Pan, Lanlan, Gao, Cuixiang, Xu, Hongtao, Li, Yanping, Zhang, Lihu, Ma, Linwei, Meng, Li, Sun, Xiulan, Qin, Hongbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572074/
https://www.ncbi.nlm.nih.gov/pubmed/31137633
http://dx.doi.org/10.3390/molecules24101993
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author Wu, Hongyan
Pan, Lanlan
Gao, Cuixiang
Xu, Hongtao
Li, Yanping
Zhang, Lihu
Ma, Linwei
Meng, Li
Sun, Xiulan
Qin, Hongbing
author_facet Wu, Hongyan
Pan, Lanlan
Gao, Cuixiang
Xu, Hongtao
Li, Yanping
Zhang, Lihu
Ma, Linwei
Meng, Li
Sun, Xiulan
Qin, Hongbing
author_sort Wu, Hongyan
collection PubMed
description Increased glycolysis in tumor cells is associated with increased risk of tumor progression and mortality. Therefore, disruption of glycolysis, one of the main sources of cellular energy supply, can serve as a target for suppressing tumor growth and progression. Of note, hexokinase-2 (HK2) plays vital roles in glucose metabolism. Moreover, the expression of HK2 alters the metabolic phenotype and supports the continuous growth of tumor cells, making it an attractive target for cancer therapy. Quercetin (QUE), a bioactive flavonoid, has a profound anti-tumor effect on hepatocellular carcinoma (HCC), but the precise underlying mechanism of this effect is unclear. In the present study, we reported that QUE inhibited the proliferation of HCC cells that relied on aerobic glycolysis. We further found that QUE could decrease the protein levels of HK2 and suppress the AKT/mTOR pathway in HCC cells. In addition, QUE significantly restrained the growth of HCC xenografts and decreased HK-2 expression in vivo. Taken together, we have revealed that QUE suppresses the progression of HCC by inhibiting HK2-dependentglycolysis, which may have a promising potential to be an effective treatments for HCC, especially for those patients with high HK2 expression.
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spelling pubmed-65720742019-06-18 Quercetin Inhibits the Proliferation of Glycolysis-Addicted HCC Cells by Reducing Hexokinase 2 and Akt-mTOR Pathway Wu, Hongyan Pan, Lanlan Gao, Cuixiang Xu, Hongtao Li, Yanping Zhang, Lihu Ma, Linwei Meng, Li Sun, Xiulan Qin, Hongbing Molecules Article Increased glycolysis in tumor cells is associated with increased risk of tumor progression and mortality. Therefore, disruption of glycolysis, one of the main sources of cellular energy supply, can serve as a target for suppressing tumor growth and progression. Of note, hexokinase-2 (HK2) plays vital roles in glucose metabolism. Moreover, the expression of HK2 alters the metabolic phenotype and supports the continuous growth of tumor cells, making it an attractive target for cancer therapy. Quercetin (QUE), a bioactive flavonoid, has a profound anti-tumor effect on hepatocellular carcinoma (HCC), but the precise underlying mechanism of this effect is unclear. In the present study, we reported that QUE inhibited the proliferation of HCC cells that relied on aerobic glycolysis. We further found that QUE could decrease the protein levels of HK2 and suppress the AKT/mTOR pathway in HCC cells. In addition, QUE significantly restrained the growth of HCC xenografts and decreased HK-2 expression in vivo. Taken together, we have revealed that QUE suppresses the progression of HCC by inhibiting HK2-dependentglycolysis, which may have a promising potential to be an effective treatments for HCC, especially for those patients with high HK2 expression. MDPI 2019-05-24 /pmc/articles/PMC6572074/ /pubmed/31137633 http://dx.doi.org/10.3390/molecules24101993 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Hongyan
Pan, Lanlan
Gao, Cuixiang
Xu, Hongtao
Li, Yanping
Zhang, Lihu
Ma, Linwei
Meng, Li
Sun, Xiulan
Qin, Hongbing
Quercetin Inhibits the Proliferation of Glycolysis-Addicted HCC Cells by Reducing Hexokinase 2 and Akt-mTOR Pathway
title Quercetin Inhibits the Proliferation of Glycolysis-Addicted HCC Cells by Reducing Hexokinase 2 and Akt-mTOR Pathway
title_full Quercetin Inhibits the Proliferation of Glycolysis-Addicted HCC Cells by Reducing Hexokinase 2 and Akt-mTOR Pathway
title_fullStr Quercetin Inhibits the Proliferation of Glycolysis-Addicted HCC Cells by Reducing Hexokinase 2 and Akt-mTOR Pathway
title_full_unstemmed Quercetin Inhibits the Proliferation of Glycolysis-Addicted HCC Cells by Reducing Hexokinase 2 and Akt-mTOR Pathway
title_short Quercetin Inhibits the Proliferation of Glycolysis-Addicted HCC Cells by Reducing Hexokinase 2 and Akt-mTOR Pathway
title_sort quercetin inhibits the proliferation of glycolysis-addicted hcc cells by reducing hexokinase 2 and akt-mtor pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572074/
https://www.ncbi.nlm.nih.gov/pubmed/31137633
http://dx.doi.org/10.3390/molecules24101993
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