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Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma
Most cancers rely disproportionately on glycolysis for energy even in the presence of an adequate oxygen supply, a condition known as “aerobic glycolysis,” or the “Warburg effect.” Pyruvate dehydrogenase E1α subunit (PDHA1) is one of the main factors for the metabolic switch from oxidative phosphory...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Cognizant Communication Corporation
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848459/ https://www.ncbi.nlm.nih.gov/pubmed/29444744 http://dx.doi.org/10.3727/096504018X15180451872087 |
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author | Sun, Jihong Li, Jingjing Guo, Zhixian Sun, Lu Juan, Chenghui Zhou, Yubing Gu, Hongli Yu, Yan Hu, Qiuyue Kan, Quancheng’ Yu, Zujiang |
author_facet | Sun, Jihong Li, Jingjing Guo, Zhixian Sun, Lu Juan, Chenghui Zhou, Yubing Gu, Hongli Yu, Yan Hu, Qiuyue Kan, Quancheng’ Yu, Zujiang |
author_sort | Sun, Jihong |
collection | PubMed |
description | Most cancers rely disproportionately on glycolysis for energy even in the presence of an adequate oxygen supply, a condition known as “aerobic glycolysis,” or the “Warburg effect.” Pyruvate dehydrogenase E1α subunit (PDHA1) is one of the main factors for the metabolic switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis and has been suggested to be closely associated with tumorigenesis. Here we observed that the PDHA1 protein was reduced in hepatocellular carcinoma (HCC) specimens by immunohistochemistry and Western blot, which was significantly associated with poor overall survival. To further analyze the function of PDHA1 in cancer cells, PDHA1 was upregulated in the HCC cell lines SMMC-7721 and HepG2. The results demonstrated that overexpression of the PDHA1 gene inhibited aerobic glycolysis with lower lactate via increased PDH activity; meanwhile, mitochondrial OXPHOS was enhanced accompanied with higher ATP and lower glucose consumption. We also found that apoptosis was promoted and intrinsic pathway proteins were increased in PDHA1-overexpressing cells. Collectively, our data indicate that reduced PDHA1 protein expression is associated with the poor clinical outcome of HCC. Upregulated PDHA1 gene expression can inhibit the Warburg effect and enhance the mitochondria-mediated apoptosis pathway. |
format | Online Article Text |
id | pubmed-7848459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Cognizant Communication Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-78484592021-02-16 Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma Sun, Jihong Li, Jingjing Guo, Zhixian Sun, Lu Juan, Chenghui Zhou, Yubing Gu, Hongli Yu, Yan Hu, Qiuyue Kan, Quancheng’ Yu, Zujiang Oncol Res Article Most cancers rely disproportionately on glycolysis for energy even in the presence of an adequate oxygen supply, a condition known as “aerobic glycolysis,” or the “Warburg effect.” Pyruvate dehydrogenase E1α subunit (PDHA1) is one of the main factors for the metabolic switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis and has been suggested to be closely associated with tumorigenesis. Here we observed that the PDHA1 protein was reduced in hepatocellular carcinoma (HCC) specimens by immunohistochemistry and Western blot, which was significantly associated with poor overall survival. To further analyze the function of PDHA1 in cancer cells, PDHA1 was upregulated in the HCC cell lines SMMC-7721 and HepG2. The results demonstrated that overexpression of the PDHA1 gene inhibited aerobic glycolysis with lower lactate via increased PDH activity; meanwhile, mitochondrial OXPHOS was enhanced accompanied with higher ATP and lower glucose consumption. We also found that apoptosis was promoted and intrinsic pathway proteins were increased in PDHA1-overexpressing cells. Collectively, our data indicate that reduced PDHA1 protein expression is associated with the poor clinical outcome of HCC. Upregulated PDHA1 gene expression can inhibit the Warburg effect and enhance the mitochondria-mediated apoptosis pathway. Cognizant Communication Corporation 2019-03-29 /pmc/articles/PMC7848459/ /pubmed/29444744 http://dx.doi.org/10.3727/096504018X15180451872087 Text en Copyright © 2019 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License. |
spellingShingle | Article Sun, Jihong Li, Jingjing Guo, Zhixian Sun, Lu Juan, Chenghui Zhou, Yubing Gu, Hongli Yu, Yan Hu, Qiuyue Kan, Quancheng’ Yu, Zujiang Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma |
title | Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma |
title_full | Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma |
title_fullStr | Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma |
title_full_unstemmed | Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma |
title_short | Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma |
title_sort | overexpression of pyruvate dehydrogenase e1α subunit inhibits warburg effect and induces cell apoptosis through mitochondria-mediated pathway in hepatocellular carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848459/ https://www.ncbi.nlm.nih.gov/pubmed/29444744 http://dx.doi.org/10.3727/096504018X15180451872087 |
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