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

Ran Wei, Natalia E. Cortez Penso, Robert M. Hackman, Yuefei Wang, Gerardo Mackenzie

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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.

Original languageEnglish (US)
Article number1856
JournalNutrients
Volume11
Issue number8
DOIs
StatePublished - Aug 1 2019

Fingerprint

gemcitabine
pancreatic neoplasms
epigallocatechin
Pancreatic Neoplasms
cell growth
Growth
Cell Movement
cell invasion
cell movement
Catenins
acetylcysteine
cadherins
vimentin
Acetylcysteine
Vimentin
green tea
Tea
Cadherins
epigallocatechin gallate
neoplasm cells

Keywords

  • Akt
  • EMT
  • Epigallocatechin-3-gallate
  • Gemcitabine
  • Pancreatic cancer

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

Cite this

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title = "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",
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.",
keywords = "Akt, EMT, Epigallocatechin-3-gallate, Gemcitabine, Pancreatic cancer",
author = "Ran Wei and {Cortez Penso}, {Natalia E.} and Hackman, {Robert M.} and Yuefei Wang and Gerardo Mackenzie",
year = "2019",
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TY - JOUR

T1 - Epigallocatechin-3-gallate (Egcg) suppresses pancreatic cancer cell growth, invasion, and migration partly through the inhibition of akt pathway and epithelial–mesenchymal transition

T2 - Enhanced efficacy when combined with gemcitabine

AU - Wei, Ran

AU - Cortez Penso, Natalia E.

AU - Hackman, Robert M.

AU - Wang, Yuefei

AU - Mackenzie, Gerardo

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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.

AB - 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.

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KW - EMT

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