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Open AccessArticle

Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts

1
Tea Science Institute, Zhejiang University, Hangzhou 310058, China
2
Department of Nutrition, University of California, Davis, CA 95616, USA
3
Davis Comprehensive Cancer Center, University of California, Sacramento, CA 95817, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(10), 1496; https://doi.org/10.3390/cancers11101496
Received: 22 August 2019 / Revised: 26 September 2019 / Accepted: 3 October 2019 / Published: 5 October 2019
(This article belongs to the Special Issue Role of Natural Bioactive Compounds in the Rise and Fall of Cancers)
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. View Full-Text
Keywords: pancreatic cancer; epigallocatechin-3-gallate (EGCG); gemcitabine; glycolysis; ROS; phosphofructokinase pancreatic cancer; epigallocatechin-3-gallate (EGCG); gemcitabine; glycolysis; ROS; phosphofructokinase
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Wei, R.; Hackman, R.M.; Wang, Y.; Mackenzie, G.G. Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts. Cancers 2019, 11, 1496.

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