Epicatechin-3-gallate reverses TGF-β1-induced epithelial-to-mesenchymal transition and inhibits cell invasion and protease activities in human lung cancer cells

Food Chem Toxicol. 2016 Aug:94:1-10. doi: 10.1016/j.fct.2016.05.009. Epub 2016 May 17.

Abstract

Epithelial-to-mesenchymal transition (EMT) and invasion potential have been considered as essential factors in cancer metastasis, which is the major cause of cancer death. EMT is a multi-step process that involves gain invasion, cytoskeleton change, cell adhesion, and proteolytic extracellular matrix degradation. Epicatechin-3-gallate (ECG), which is a natural polyphenolic component of green tea, elicits several antioxidant and anti-inflammatory effects. However, the effects of ECG on cancer invasion and EMT of human lung carcinoma remain unknown. We provided molecular evidence supporting the anti-metastatic effect of ECG. This compound suppressed the invasion (P < 0.001) of highly metastatic A549 cells by reducing the activities of matrix metalloproteinase-2 (P < 0.001) and urokinasetype plasminogen activator (P < 0.001). ECG also reversed the transforming growth factor (TGF)-β1-induced EMT and upregulated epithelial markers, such as E-cadherin. Conversely, ECG inhibited mesenchymal markers, such as fibronectin and p-FAK. The subcutaneous inoculation of this compound also inhibited the tumor growth of the A549 cells in vivo. Therefore, ECG may be used as an anti-cancer and anti-invasion agent for the adjuvant treatment and metastasis control of human lung cancer cells. ECG may also be administered as an effective chemopreventive agent against TGF-β1-induced EMT.

Keywords: ECG; EMT; Lung cancer; Metastasis; Polyphenol.

MeSH terms

  • Animals
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition / physiology*
  • Heterografts
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Matrix Metalloproteinase 2 / metabolism*
  • Mice
  • Neoplasm Invasiveness / prevention & control*
  • Signal Transduction
  • Transforming Growth Factor beta1 / antagonists & inhibitors*
  • Transforming Growth Factor beta1 / physiology

Substances

  • Transforming Growth Factor beta1
  • Catechin
  • epicatechin gallate
  • Matrix Metalloproteinase 2