Tea polyphenol (-)-epigallocatechin-3-gallate inhibits nicotine- and estrogen-induced α9-nicotinic acetylcholine receptor upregulation in human breast cancer cells

Shih Hsin Tu, Chung Yu Ku, Chi Tang Ho, Ching Shyang Chen, Ching Shui Huang, Chia Hwa Lee, Li Ching Chen, Min Hsiung Pan, Hui Wen Chang, Chien Hsi Chang, Yu Jia Chang, Po Li Wei, Chih Hsiung Wu, Yuan Soon Ho

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)455-466
Number of pages12
JournalMolecular Nutrition and Food Research
Volume55
Issue number3
DOIs
Publication statusPublished - Mar 2011

Keywords

  • (-)-Epigallocatechin-3-gallate
  • Breast cancer
  • Estradiol
  • Nicotine
  • Nicotinic acetylcholine receptor

ASJC Scopus subject areas

  • Food Science
  • Biotechnology

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