These authors have contributed equally to this work.
Tea polyphenol (−)-epigallocatechin-3-gallate inhibits nicotine- and estrogen-induced α9-nicotinic acetylcholine receptor upregulation in human breast cancer cells
Article first published online: 28 OCT 2010
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 55, Issue 3, pages 455–466, March 2011
How to Cite
Tu, S.-H., Ku, C.-Y., Ho, C.-T., Chen, C.-S., Huang, C.-S., Lee, C.-H., Chen, L.-C., Pan, M.-H., Chang, H.-W., Chang, C.-H., Chang, Y.-J., Wei, P.-L., Wu, C.-H. and Ho, Y.-S. (2011), Tea polyphenol (−)-epigallocatechin-3-gallate inhibits nicotine- and estrogen-induced α9-nicotinic acetylcholine receptor upregulation in human breast cancer cells. Mol. Nutr. Food Res., 55: 455–466. doi: 10.1002/mnfr.201000254
- Issue published online: 2 MAR 2011
- Article first published online: 28 OCT 2010
- Manuscript Accepted: 3 SEP 2010
- Manuscript Revised: 8 AUG 2010
- Manuscript Received: 3 JUN 2010
- National Science Council. Grant Numbers: NSC 96-2628-B-038-003-MY3(1-3, NSC 98-2320-B-038-006-MY3(1-3, DOH99-TD-C-111-008, NSC 97-2314-B-038-034-MY3(1-3
- Cathay Medical Center. Grant Numbers: 96CGH-TMU-02, 97CGH-TMU-02
- Breast cancer;
- Nicotinic acetylcholine receptor
Scope: The aim of this research was to explore whether the tea-polyphenol (–)-epigallocatechin-3-gallate (EGCG) could be used as a potential agent for blocking smoking (nicotine, Nic)- or hormone (estradiol, E2)-induced breast cancer cell proliferation through inhibition of a common signaling pathway.
Methods and results: To explore whether Nic (>0.1 μM, 24 h) and E2 (>1 nM, 24 h) significantly increased α9-nicotinic acetylcholine (α9-nicotinic acetylcholine receptor (nAChR)) mRNA and protein expression levels, real-time PCR and immunoblotting analysis experiments were performed in human breast cancer (MCF-7) cells. Luciferase promoter activity experiment was performed to test the α9-nAChR promoter activity affected by Nic, E2 or EGCG. The results indicate that treatment with EGCG (1 μM) profoundly decreases Nic- and E2-induced MCF-7 proliferation by down regulating α9-nAChR expression. The α9-nAChR promoter activity is significantly induced by 24-h treatment with Nic (10 μM) or E2 (10 nM) (>1.8 and ∼2.3-fold, respectively) in MCF-7 cells. Pretreatment with EGCG eliminated the Nic- and E2-induced α9-nAChR promoter-dependent luciferase activity. We further demonstrate that combined treatment with EGCG profoundly inhibits [3H]-Nic/ α9-nAChR binding activity in breast cancer cells.
Conclusions: We found that the EGCG could be used as an agent for blocking smoking (Nic)- or hormone (E2)-induced breast cancer cell proliferation by inhibiting of α9-nAChR signaling pathway. This study reveals the novel antitumor mechanisms of EGCG, and these results may have significant applications for chemopreventive purposes in human breast cancer.