EGCG inhibits transforming growth factor-β-mediated epithelial-to-mesenchymal transition via the inhibition of smad2 and Erk1/2 signaling pathways in nonsmall cell lung cancer cells

Liang Chih Liu, Thomas Chang Yao Tsao, Shu Rong Hsu, Hwei Chung Wang, Tsuen Chiuan Tsai, Jung Yie Kao*, Tzong Der Way

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

64 Scopus citations

Abstract

Transforming growth factor-β (TGF-β)-mediated epithelial mesenchymal transition (EMT) of human lung cancer cells may contribute to lung cancer metastasis. It has been reported that EGCG can inhibit tumorigenesis and cancer cell growth in lung cancer; however, the effect of EGCG on EMT in nonsmall cell lung cancer (NSCLC) cells has not been investigated. In this study, we found that NSCLC cells A549 and H1299 were converted to the fibroblastic phenotype in response to TGF-β. Epithelial marker E-cadherin was down-regulated, and mesenchymal marker vimentin was up-regulated simultaneously. Our results illustrated that TGF-β was able to induce EMT in NSCLC cells, and EGCG would reverse TGF-β-induced morphological changes, up-regulate the expression of E-cadherin, and down-regulate the expression of vimentin. Immunofluorescent staining also demonstrated that E-cadherin was up-regulated and that vimentin was down-regulated by EGCG pretreatment. Moreover, wound-healing and the in vitro invasion assay showed that EGCG could inhibit TGF-β-induced migration and invasion of NSCLC cells. By using the dual-luciferase reporter assay, we demonstrated that EGCG inhibited TGF-β-induced EMT at the transcriptional level. EGCG decreased the phosphorylation of Smad2 and Erk1/2, inhibited the nuclear translocation of Smad2, and repressed the expression of transcription factors ZEB1, Snail, Slug, and Twist, and up-regulated the expression of E-cadherin. In summary, our results suggest that EGCG can inhibit TGF-β-induced EMT via down-regulation of phosphorylated Smad2 and Erk1/2 in NSCLC cells.

Original languageEnglish
Pages (from-to)9863-9873
Number of pages11
JournalJournal of Agricultural and Food Chemistry
Volume60
Issue number39
DOIs
StatePublished - 03 10 2012
Externally publishedYes

Keywords

  • EGCG
  • EMT
  • Smad2
  • TGF-β
  • nonsmall cell lung cancer

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