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

• Published in: Nutrients Vol. 11; no. 8; p. 1856
• Main Authors: Wei, Ran, Penso, Natalia E Cortez, Hackman, Robert M, Wang, Yuefei, Mackenzie, Gerardo G
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09-08-2019; MDPI
• Subjects: Akt; AKT protein; Animals; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Biocompatibility; Cancer therapies; Catechin - analogs & derivatives; Catechin - pharmacology; Cell adhesion & migration; Cell culture; Cell cycle; Cell death; Cell growth; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; EMT; Enzyme Stability; Epigallocatechin gallate; epigallocatechin-3-gallate; Epithelial-Mesenchymal Transition - drug effects; Gemcitabine; Growth factors; Humans; Membranes; Mesenchyme; Metastasis; Mice, Inbred C57BL; Motility; Neoplasm Invasiveness; Oxidation; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - enzymology; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Proteolysis; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; Systematic review; Toxicity; Tumor Burden; Tumors; St Louis Missouri; New York; United States > US; epigallocatechin-3-gallate; pancreatic cancer; gemcitabine; Akt; EMT
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu11081856

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.