Tu_2011_Mol.Nutr.Food.Res_55_455

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 muM, 24 h) and E2 (>1 nM, 24 h) significantly increased alpha9-nicotinic acetylcholine (alpha9-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 alpha9-nAChR promoter activity affected by Nic, E2 or EGCG. The results indicate that treatment with EGCG (1 muM) profoundly decreases Nic- and E2-induced MCF-7 proliferation by down regulating alpha9-nAChR expression. The alpha9-nAChR promoter activity is significantly induced by 24-h treatment with Nic (10 muM) or E2 (10 nM) (>1.8 and approximately 2.3-fold, respectively) in MCF-7 cells. Pretreatment with EGCG eliminated the Nic- and E2-induced alpha9-nAChR promoter-dependent luciferase activity. We further demonstrate that combined treatment with EGCG profoundly inhibits [3H]-Nic/ alpha9-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 alpha9-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.