EGCG inhibits the invasion of highly invasive CL1-5 lung cancer cells through suppressing MMP-2 expression via JNK signaling and induces G2/M arrest

J Agric Food Chem. 2011 Dec 28;59(24):13318-27. doi: 10.1021/jf204149c. Epub 2011 Nov 30.


Tumor metastasis is the main obstacle to the treatment of lung cancer. According to previous findings, matrix metalloproteinase-2 (MMP-2) is closely correlated with metastatic potential in lung cancer. This study showed that epigallocatechin-3-gallate (EGCG), a natural polyphenol in green tea, is a potent inhibitor of MMP-2 expression. EGCG effectively suppressed the invasion and migration of highly invasive CL1-5 lung cancer cells. Gelatin zymography, Western blot analysis, and RT-PCR were used to investigate the effects of EGCG on MMP-2 expression. The effects of EGCG on cell cycle and apoptosis were determined by flow cytometry analysis. To investigate the effects of EGCG on cell migration and cell invasion, Transwell migration/invasion assays were used. EGCG downregulated MMP-2 expression at the transcriptional level in CL1-5 cells. Moreover, the treatment of CL1-5 cells with EGCG caused downregulation of c- Jun N-terminal kinase (JNK), resulting in repression of the translocation of transcriptional factors, Sp1, and NF-κB, from the cytosol into the nucleus. In addition, EGCG significantly and synergistically enhanced the antitumor effects of the clinical drug, docetaxel, in CL1-5 cells. Further, EGCG induced G2/M arrest at dosages higher than those of suppression in cell invasion in CL1-5 cells. These results reveal that EGCG might decrease MMP-2 mRNA expression through JNK signaling, further suggesting that a combination of EGCG and docetaxel may be a promising strategy to help increase the efficacy of docetaxel in suppressing metastasis in lung cancer cells. In addition, EGCG may suppress cell proliferation in CL1-5 cells through inducing G2/M arrest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents
  • Apoptosis / drug effects
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Line, Tumor
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Gene Expression / drug effects*
  • Humans
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / pathology*
  • M Phase Cell Cycle Checkpoints / drug effects
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / physiology
  • Matrix Metalloproteinase 2 / genetics*
  • Neoplasm Invasiveness / prevention & control*
  • Tea


  • Anticarcinogenic Agents
  • Tea
  • Catechin
  • epigallocatechin gallate
  • Matrix Metalloproteinase 2