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Inhibition of pyruvate dehydrogenase kinase-1 by dicoumarol enhances the sensitivity of hepatocellular carcinoma cells to oxaliplatin via metabolic reprogramming
The Warburg effect is a unique metabolic feature of the majority of tumor cells and is closely related to chemotherapeutic resistance. Pyruvate dehydrogenase kinase 1 (PDK1) is considered a 'switch' that controls the fate of pyruvate in glucose metabolism. However, to date, to the best of...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384842/ https://www.ncbi.nlm.nih.gov/pubmed/32705170 http://dx.doi.org/10.3892/ijo.2020.5098 |
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author | Xu, Huadan He, Yichun Ma, Jiaoyan Zhao, Yuanxin Liu, Yanan Sun, Liankun Su, Jing |
author_facet | Xu, Huadan He, Yichun Ma, Jiaoyan Zhao, Yuanxin Liu, Yanan Sun, Liankun Su, Jing |
author_sort | Xu, Huadan |
collection | PubMed |
description | The Warburg effect is a unique metabolic feature of the majority of tumor cells and is closely related to chemotherapeutic resistance. Pyruvate dehydrogenase kinase 1 (PDK1) is considered a 'switch' that controls the fate of pyruvate in glucose metabolism. However, to date, to the best of our knowledge, there are only a few studies to available which had studied the reduction of chemotherapeutic resistance via the metabolic reprogramming of tumor cells with PDK1 as a target. In the present study, it was found dicoumarol (DIC) reduced the phosphorylation of pyruvate dehydrogenase (PDH) by inhibiting the activity of PDK1, which converted the metabolism of human hepatocellular carcinoma (HCC) cells to oxidative phosphorylation, leading to an increase in mitochondrial reactive oxygen species ROS (mtROS) and a decrease in mitochondrial membrane potential (MMP), thereby increasing the apoptosis induced by oxaliplatin (OXA). Furthermore, the present study elucidated that the targeting of PDK1 may be a potential strategy for targeting metabolism in the chemotherapy of HCC. In addition, DIC as an 'old drug' exhibits novel efficacy, bringing new hope for antitumor therapy. |
format | Online Article Text |
id | pubmed-7384842 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-73848422020-07-30 Inhibition of pyruvate dehydrogenase kinase-1 by dicoumarol enhances the sensitivity of hepatocellular carcinoma cells to oxaliplatin via metabolic reprogramming Xu, Huadan He, Yichun Ma, Jiaoyan Zhao, Yuanxin Liu, Yanan Sun, Liankun Su, Jing Int J Oncol Articles The Warburg effect is a unique metabolic feature of the majority of tumor cells and is closely related to chemotherapeutic resistance. Pyruvate dehydrogenase kinase 1 (PDK1) is considered a 'switch' that controls the fate of pyruvate in glucose metabolism. However, to date, to the best of our knowledge, there are only a few studies to available which had studied the reduction of chemotherapeutic resistance via the metabolic reprogramming of tumor cells with PDK1 as a target. In the present study, it was found dicoumarol (DIC) reduced the phosphorylation of pyruvate dehydrogenase (PDH) by inhibiting the activity of PDK1, which converted the metabolism of human hepatocellular carcinoma (HCC) cells to oxidative phosphorylation, leading to an increase in mitochondrial reactive oxygen species ROS (mtROS) and a decrease in mitochondrial membrane potential (MMP), thereby increasing the apoptosis induced by oxaliplatin (OXA). Furthermore, the present study elucidated that the targeting of PDK1 may be a potential strategy for targeting metabolism in the chemotherapy of HCC. In addition, DIC as an 'old drug' exhibits novel efficacy, bringing new hope for antitumor therapy. D.A. Spandidos 2020-07-10 /pmc/articles/PMC7384842/ /pubmed/32705170 http://dx.doi.org/10.3892/ijo.2020.5098 Text en Copyright: © Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Xu, Huadan He, Yichun Ma, Jiaoyan Zhao, Yuanxin Liu, Yanan Sun, Liankun Su, Jing Inhibition of pyruvate dehydrogenase kinase-1 by dicoumarol enhances the sensitivity of hepatocellular carcinoma cells to oxaliplatin via metabolic reprogramming |
title | Inhibition of pyruvate dehydrogenase kinase-1 by dicoumarol enhances the sensitivity of hepatocellular carcinoma cells to oxaliplatin via metabolic reprogramming |
title_full | Inhibition of pyruvate dehydrogenase kinase-1 by dicoumarol enhances the sensitivity of hepatocellular carcinoma cells to oxaliplatin via metabolic reprogramming |
title_fullStr | Inhibition of pyruvate dehydrogenase kinase-1 by dicoumarol enhances the sensitivity of hepatocellular carcinoma cells to oxaliplatin via metabolic reprogramming |
title_full_unstemmed | Inhibition of pyruvate dehydrogenase kinase-1 by dicoumarol enhances the sensitivity of hepatocellular carcinoma cells to oxaliplatin via metabolic reprogramming |
title_short | Inhibition of pyruvate dehydrogenase kinase-1 by dicoumarol enhances the sensitivity of hepatocellular carcinoma cells to oxaliplatin via metabolic reprogramming |
title_sort | inhibition of pyruvate dehydrogenase kinase-1 by dicoumarol enhances the sensitivity of hepatocellular carcinoma cells to oxaliplatin via metabolic reprogramming |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384842/ https://www.ncbi.nlm.nih.gov/pubmed/32705170 http://dx.doi.org/10.3892/ijo.2020.5098 |
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