論文

査読有り
2005年4月

(-)-epigallocatechin gallate and polyphenon E inhibit growth and activation of the epidermal growth factor receptor and human epidermal growth factor receptor-2 signaling pathways in human colon cancer cells

CLINICAL CANCER RESEARCH
  • M Shimizu
  • ,
  • A Deguchi
  • ,
  • JTE Lim
  • ,
  • H Moriwaki
  • ,
  • L Kopelovich
  • ,
  • IB Weinstein

11
7
開始ページ
2735
終了ページ
2746
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1158/1078-0432.CCR-04-2014
出版者・発行元
AMER ASSOC CANCER RESEARCH

Purpose: (-)-Epigallocatechin gallate (EGCG) inhibits activation of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER2) and multiple downstream signaling pathways in cancer cell lines. In this study we compared the cellular and molecular effects of EGCG with a well-standardized decaffeinated green tea catechin mixture Polyphenon E (Poly E) on human colon cancer cell lines.
Experimental Design and Results: Both EGCG and Poly E preferentially inhibited growth of the Caco2, HCT116, HT29, SW480, and SW837 colon cancer cells when compared with the FHC normal human fetal colon cell line. The EGFR and HER2 proteins were overexpressed and constitutively activated in all of the colon cancer cell lines when compared with the FHC cell line. Treatment of HT29 cells with EGCG or Poly E caused an increase of cells in G(1) and induced apoptosis. Both EGCG and Poly E caused a decrease in the phosphorylated forms of EGFR and HER2 proteins, and subsequently caused a decrease in the phosphorylated forms of the extracellular signal-regulated kinase and Akt proteins. Similar effects of these compounds were seen when the cells were stimulated with transforming growth factor alpha. Reporter assays indicated that both EGCG and Poly E inhibited the transcriptional activity of the activator protein 1 (AP-1), c-fos, nuclear factor kappa B, and cyclin D1 promoters. The combination of only 1 mu g/mL of epicatechin plus 10 mu g/mL of EGCG displayed synergistic effects on growth inhibition and induction of apoptosis. Furthermore, when treatment was prolonged for 96 hours, 1 mu g/mL of EGCG or Poly E was sufficient to inhibit growth, reduce activation of EGFR and HER2, and induce apoptosis.
Conclusion: Our findings suggest that EGCG or Poly E may be useful in the chemoprevention and/or treatment of colon cancer. Poly E contains about 60% EGCG, yet pure EGCG and Poly E had similar potencies (expressed as mu g/mL). Poly E may be preferable because it is easier to prepare and this mixture of catechins may exert synergistic effects.

Web of Science ® 被引用回数 : 251

リンク情報
DOI
https://doi.org/10.1158/1078-0432.CCR-04-2014
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/15814656
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000228320100038&DestApp=WOS_CPL

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