Tea Polyphenol (-)-epigallocatechin-3-gallate Inhibits Nicotine- And Estrogen-Induced α9-nicotinic Acetylcholine Receptor Upregulation in Human Breast Cancer Cells

Mol Nutr Food Res. 2011 Mar;55(3):455-66. doi: 10.1002/mnfr.201000254. Epub 2010 Oct 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Hormonal / pharmacology*
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation
  • Estrogens
  • Female
  • Flavonoids / pharmacology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Nicotine / metabolism
  • Nicotinic Antagonists / pharmacology*
  • Phenols / pharmacology*
  • Polyphenols
  • RNA, Messenger / metabolism
  • Receptors, Nicotinic / metabolism*
  • Signal Transduction
  • Tea / chemistry*
  • Up-Regulation

Substances

  • Antineoplastic Agents, Hormonal
  • Estrogens
  • Flavonoids
  • Nicotinic Antagonists
  • Phenols
  • Polyphenols
  • RNA, Messenger
  • Receptors, Nicotinic
  • Tea
  • nAChR alpha9
  • Nicotine
  • Catechin
  • epigallocatechin gallate