Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

The green tea catechins, (−)-Epigallocatechin-3-gallate (EGCG) and (−)-Epicatechin-3-gallate (ECG), inhibit HGF/Met signaling in immortalized and tumorigenic breast epithelial cells

Oncogene volume 25, pages 1922–1930 (2006)Cite this article

Abstract

The hepatocyte growth factor (HGF) receptor, Met, is a strong prognostic indicator of breast cancer patient outcome and survival, suggesting that therapies targeting Met may have beneficial outcomes in the clinic. (−)-Epigallocatechin-3-gallate (EGCG), a catechin found in green tea, has been recognized as a potential therapeutic agent. We assessed the ability of EGCG to inhibit HGF signaling in the immortalized, nontumorigenic breast cell line, MCF10A, and the invasive breast carcinoma cell line, MDA-MB-231. HGF treatment in both cell lines induced rapid, sustained activation of Met, ERK and AKT. Pretreatment of cells with concentrations of EGCG as low as 0.3 μ M inhibited HGF-induced Met phosphorylation and downstream activation of AKT and ERK. Treatment with 5.0 μ M EGCG blocked the ability of HGF to induce cell motility and invasion. We assessed the ability of alternative green tea catechins to inhibit HGF-induced signaling and motility. (−)-Epicatechin-3-gallate (ECG) functioned similar to EGCG by completely blocking HGF-induced signaling as low as 0.6 μ M and motility at 5 μ M in MCF10A cells; whereas, (−)-epicatechin (EC) was unable to inhibit HGF-induced events at any concentration tested. (−)-Epigallocatechin (EGC), however, completely repressed HGF-induced AKT and ERK phosphorylation at concentrations of 10 and 20 μ M, but was incapable of blocking Met activation. Despite these observations, EGC did inhibit HGF-induced motility in MCF10A cells at 10 μ M. These observations suggest that the R1 galloyl and the R2 hydroxyl groups are important in mediating the green tea catechins' inhibitory effect towards HGF/Met signaling. These combined in vitro studies reveal the possible benefits of green tea polyphenols as cancer therapeutic agents to inhibit Met signaling and potentially block invasive cancer growth.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

Abbreviations

EGCG:

(−)-epigallocatechin-3-gallate

ECG:

(−)-epicatechin gallate

EGC:

(−)-epigallocatechin

EC:

(−)-epicatechin

HGF:

hepatocyte growth factor

References

  • Adhami VM, Siddiqui IA, Ahmad N, Gupta S, Mukhtar H . (2004). Cancer Res 64: 8715–8722.

  • Berger SJ, Gupta S, Belfi CA, Gosky DM, Mukhtar H . (2001). Biochem Biophys Res Commun 288: 101–105.

  • Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF . (2003). Nat Rev Mol Cell Biol 4: 915–925.

  • Camp RL, Rimm EB, Rimm DL . (1999). Cancer 86: 2259–2265.

  • Cao Y, Cao R . (1999). Nature 398: 381.

  • Crespy V, Williamson G . (2004). J Nutr 134: 3431S–3440S.

  • Edakuni G, Sasatomi E, Satoh T, Tokunaga O, Miyazaki K . (2001). Pathol Int 51: 172–178.

  • Fang MZ, Wang Y, Ai N, Hou Z, Sun Y, Lu H et al. (2003). Cancer Res 63: 7563–7570.

  • Fujimura Y, Tachibana H, Yamada K . (2004). FEBS Lett 556: 204–210.

  • Ghoussoub RA, Dillon DA, D'Aquila T, Rimm EB, Fearon ER, Rimm DL . (1998). Cancer 82: 1513–1520.

  • Jung YD, Kim MS, Shin BA, Chay KO, Ahn BW, Liu W et al. (2001). Br J Cancer 84: 844–850.

  • Katiyar SK, Afaq F, Azizuddin K, Mukhtar H . (2001). Toxicol Appl Pharmacol 176: 110–117.

  • Kavanagh KT, Hafer LJ, Kim DW, Mann KK, Sherr DH, Rogers AE et al. (2001). J Cell Biochem 82: 387–398.

  • Lambert JD, Yang CS . (2003). J Nutr 133: 3262S–3267S.

  • Liang TJ, Reid AE, Xavier R, Cardiff RD, Wang TC . (1996). J Clin Invest 97: 2872–2877.

  • Liang YC, Lin-shiau SY, Chen CF, Lin JK . (1997). J Cell Biochem 67: 55–65.

  • Masuda M, Suzui M, Lim JT, Weinstein IB . (2003). Clin Cancer Res 9: 3486–3491.

  • Nakachi K, Suemasu K, Suga K, Takeo T, Imai K, Higashi Y . (1998). Jpn J Cancer Res 89: 254–261.

  • Nam S, Smith DM, Dou QP . (2001). J Biol Chem 276: 13322–13330.

  • Park M, Dean M, Cooper CS, Schmidt M, O'Brien SJ, Blair DG et al. (1986). Cell 45: 895–904.

  • Potempa S, Ridley AJ . (1998). Mol Biol Cell 9: 2185–2200.

  • Royal I, Park M . (1995). J Biol Chem 270: 27780–27787.

  • Sachinidis A, Seul C, Seewald S, Ahn H, Ko Y, Vetter H . (2000). FEBS Lett 471: 51–55.

  • Sah JF, Balasubramanian S, Eckert RL, Rorke EA . (2004). J Biol Chem 279: 12755–12762.

  • Su LJ, Arab L . (2002). Public Health Nutr 5: 419–425.

  • Sun CL, Yuan JM, Lee MJ, Yang CS, Gao YT, Ross RK et al. (2002). Carcinogenesis 23: 1497–1503.

  • Tachibana H, Koga K, Fujimura Y, Yamada K . (2004). Nat Struct Mol Biol 11: 380–381.

  • Tolgay Ocal I, Dolled-Filhart M, D'Aquila TG, Camp RL, Rimm DL . (2003). Cancer 97: 1841–1848.

  • Trusolino L, Comoglio PM . (2002). Nat Rev Cancer 2: 289–300.

  • Yang GY, Liao J, Kim K, Yurkow EJ, Yang CS . (1998). Carcinogenesis 19: 611–616.

  • Yang GY, Liao J, Li C, Chung J, Yurkow EJ, Ho CT et al. (2000). Carcinogenesis 21: 2035–2039.

Download references

Acknowledgements

This work was supported through Grant NIH R01 CA104242-01.

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology, Feist-Weiller Cancer Center, Louisiana State University-Health Sciences Center, Shreveport, LA, USA

    R L H Bigelow & J A Cardelli

Authors
  1. R L H Bigelow
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J A Cardelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J A Cardelli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bigelow, R., Cardelli, J. The green tea catechins, (−)-Epigallocatechin-3-gallate (EGCG) and (−)-Epicatechin-3-gallate (ECG), inhibit HGF/Met signaling in immortalized and tumorigenic breast epithelial cells. Oncogene 25, 1922–1930 (2006). https://doi.org/10.1038/sj.onc.1209227

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209227

Keywords

This article is cited by

Search

Advanced search

Quick links