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Epigallocatechin-3-Gallate (EGCG) Suppresses Pancreatic Cancer Cell Growth, Invasion, and Migration partly through the Inhibition of Akt Pathway and Epithelial–Mesenchymal Transition: Enhanced Efficacy When Combined with Gemcitabine

1
Tea Science Institute, Zhejiang University, Hangzhou 310058, China
2
Department of Nutrition, University of California, Davis, CA 95616, USA
*
Authors to whom correspondence should be addressed.
Nutrients 2019, 11(8), 1856; https://doi.org/10.3390/nu11081856
Received: 10 July 2019 / Revised: 3 August 2019 / Accepted: 6 August 2019 / Published: 9 August 2019
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Abstract

Most pancreatic cancers are usually diagnosed at an advanced stage when they have already metastasized. Epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of green tea, has been shown to reduce pancreatic cancer growth, but its effect on metastasis remains elusive. This study evaluated the capacity of EGCG to inhibit pancreatic cancer cell migration and invasion and the underlying mechanisms. EGCG reduced pancreatic cancer cell growth, migration, and invasion in vitro and in vivo. EGCG prevented “Cadherin switch” and decreased the expression level of TCF8/ZEB1, β-Catenin, and Vimentin. Mechanistically, EGCG inhibited the Akt pathway in a time-dependent manner, by suppressing IGFR phosphorylation and inducing Akt degradation. Co-treatment with catalase or N-Acetyl-L-cysteine did not abrogate EGCG’s effect on the Akt pathway or cell growth. Moreover, EGCG synergized with gemcitabine to suppress pancreatic cancer cell growth, migration, and invasion, through modulating epithelial–mesenchymal transition markers and inhibiting Akt pathway. In summary, EGCG may prove beneficial to improve gemcitabine sensitivity in inhibiting pancreatic cancer cell migration and invasion, to some extent through the inhibition of Akt pathway and epithelial–mesenchymal transition. View Full-Text
Keywords: pancreatic cancer; epigallocatechin-3-gallate; Akt; EMT; gemcitabine pancreatic cancer; epigallocatechin-3-gallate; Akt; EMT; gemcitabine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Wei, R.; Cortez Penso, N.E.; Hackman, R.M.; Wang, Y.; Mackenzie, G.G. Epigallocatechin-3-Gallate (EGCG) Suppresses Pancreatic Cancer Cell Growth, Invasion, and Migration partly through the Inhibition of Akt Pathway and Epithelial–Mesenchymal Transition: Enhanced Efficacy When Combined with Gemcitabine. Nutrients 2019, 11, 1856.

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