Black tea polyphenols reverse epithelial-to-mesenchymal transition and suppress cancer invasion and proteases in human oral cancer cells

J Agric Food Chem. 2012 Aug 29;60(34):8395-403. doi: 10.1021/jf302223g. Epub 2012 Aug 16.


Epithelial-to-mesenchymal transition (EMT) in cancer cells is considered to be a prerequisite for acquiring invasive/migratory phenotype and subsequent metastasis. This study provides molecular evidence associated with the antimetastatic effect of black tea polyphenol extracts (BTE), which contain polyphenols including gallic acid, gallocatechin, catechin, epigallocatechin-3-gallate, epicatechin-3-gallate, and theaflavin 3,3'-digallate, in an an oral squamous cell culture system by showing a nearly complete inhibition on the invasion (p < 0.001) of SCC-4 cells via reduced activities of MMP-2 (p < 0.001) and u-PA (p < 0.001). Immunoblot was performed to find that BTE could induce up-regulation of epithelial markers such as E-cadherin and inhibit mesenchymal markers such as snail-1 and vimentin. BTE inhibited p-FAK and p-paxillin, indicating the anti-EMT effect of BTE in oral squamous cell carcinoma. BTE was evidenced by its inhibition of the tumor growth of SCC-4 cells via cancer cell xenografted nude mice mode. These results suggested that BTE could reduce invasion by reversing EMT in human oral cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Camellia sinensis / chemistry*
  • Cell Movement / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / physiology
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Mice
  • Mice, Nude
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Neoplasms, Squamous Cell / drug therapy*
  • Neoplasms, Squamous Cell / metabolism
  • Neoplasms, Squamous Cell / pathology
  • Polyphenols / pharmacology*
  • Promoter Regions, Genetic / drug effects
  • Protease Inhibitors / pharmacology
  • Tumor Cells, Cultured
  • Urokinase-Type Plasminogen Activator / genetics
  • Urokinase-Type Plasminogen Activator / metabolism
  • Vimentin / antagonists & inhibitors
  • Vimentin / metabolism
  • Xenograft Model Antitumor Assays


  • Cadherins
  • Polyphenols
  • Protease Inhibitors
  • Vimentin
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinase 2