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Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts
Pancreatic cancer is a complex disease, in need of new therapeutic approaches. In this study, we explored the effect and mechanism of action of epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, alone and in combination with current chemotherapeutics on pancreatic cancer cell growth...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826788/ https://www.ncbi.nlm.nih.gov/pubmed/31590367 http://dx.doi.org/10.3390/cancers11101496 |
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author | Wei, Ran Hackman, Robert M. Wang, Yuefei Mackenzie, Gerardo G. |
author_facet | Wei, Ran Hackman, Robert M. Wang, Yuefei Mackenzie, Gerardo G. |
author_sort | Wei, Ran |
collection | PubMed |
description | Pancreatic cancer is a complex disease, in need of new therapeutic approaches. In this study, we explored the effect and mechanism of action of epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, alone and in combination with current chemotherapeutics on pancreatic cancer cell growth, focusing on glycolysis metabolism. Moreover, we investigated whether EGCG’s effect is dependent on its ability to induce reactive oxygen species (ROS). EGCG reduced pancreatic cancer cell growth in a concentration-dependent manner and the growth inhibition effect was further enhanced under glucose deprivation conditions. Mechanistically, EGCG induced ROS levels concentration-dependently. EGCG affected glycolysis by suppressing the extracellular acidification rate through the reduction of the activity and levels of the glycolytic enzymes phosphofructokinase and pyruvate kinase. Cotreatment with catalase abrogated EGCG’s effect on phosphofructokinase and pyruvate kinase. Furthermore, EGCG sensitized gemcitabine to inhibit pancreatic cancer cell growth in vitro and in vivo. EGCG and gemcitabine, given alone, reduced pancreatic tumor xenograft growth by 40% and 52%, respectively, whereas the EGCG/gemcitabine combination reduced tumor growth by 67%. EGCG enhanced gemcitabine’s effect on apoptosis, cell proliferation, cell cycle and further suppressed phosphofructokinase and pyruvate kinase levels. In conclusion, EGCG is a strong combination partner of gemcitabine reducing pancreatic cancer cell growth by suppressing glycolysis. |
format | Online Article Text |
id | pubmed-6826788 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68267882019-11-18 Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts Wei, Ran Hackman, Robert M. Wang, Yuefei Mackenzie, Gerardo G. Cancers (Basel) Article Pancreatic cancer is a complex disease, in need of new therapeutic approaches. In this study, we explored the effect and mechanism of action of epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, alone and in combination with current chemotherapeutics on pancreatic cancer cell growth, focusing on glycolysis metabolism. Moreover, we investigated whether EGCG’s effect is dependent on its ability to induce reactive oxygen species (ROS). EGCG reduced pancreatic cancer cell growth in a concentration-dependent manner and the growth inhibition effect was further enhanced under glucose deprivation conditions. Mechanistically, EGCG induced ROS levels concentration-dependently. EGCG affected glycolysis by suppressing the extracellular acidification rate through the reduction of the activity and levels of the glycolytic enzymes phosphofructokinase and pyruvate kinase. Cotreatment with catalase abrogated EGCG’s effect on phosphofructokinase and pyruvate kinase. Furthermore, EGCG sensitized gemcitabine to inhibit pancreatic cancer cell growth in vitro and in vivo. EGCG and gemcitabine, given alone, reduced pancreatic tumor xenograft growth by 40% and 52%, respectively, whereas the EGCG/gemcitabine combination reduced tumor growth by 67%. EGCG enhanced gemcitabine’s effect on apoptosis, cell proliferation, cell cycle and further suppressed phosphofructokinase and pyruvate kinase levels. In conclusion, EGCG is a strong combination partner of gemcitabine reducing pancreatic cancer cell growth by suppressing glycolysis. MDPI 2019-10-05 /pmc/articles/PMC6826788/ /pubmed/31590367 http://dx.doi.org/10.3390/cancers11101496 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 Wei, Ran Hackman, Robert M. Wang, Yuefei Mackenzie, Gerardo G. Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts |
title | Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts |
title_full | Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts |
title_fullStr | Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts |
title_full_unstemmed | Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts |
title_short | Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts |
title_sort | targeting glycolysis with epigallocatechin-3-gallate enhances the efficacy of chemotherapeutics in pancreatic cancer cells and xenografts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826788/ https://www.ncbi.nlm.nih.gov/pubmed/31590367 http://dx.doi.org/10.3390/cancers11101496 |
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