Tea Extracts Confer Its Antiproliferating Effects Through Inhibition of Nicotine- and Estrogen-induced 9-Nicotinic Acetylcholine Receptor Upregulation in Human Breast Cancer Cells Check Access

We have previously demonstrated that the tea-polyphenol (-)-epigallocatechin-3-gallate (EGCG) could be used as an agent for blocking smoking (nicotine, Nic)- or hormone (estradiol, E2)-induced breast cancer cell proliferation by inhibiting a common signaling pathway. We found that Nic (>0.1 μM, 24 h) and E2 (>1 nM, 24 h) significantly increased α9-nicotinic acetylcholine (α9-nAChR) mRNA and protein expression levels in human breast cancer (MCF-7) cells. We then hypothesized that green tea and black tea-extract ingredients (TEIs) with inhibitory effects on α9-nAChR protein levels could be used to block the Nic- or E2-mediated carcinogenic signals. Our previous results indicated that treatment with EGCG (1 μM) profoundly decreased Nic- and E2-induced MCF-7 proliferation by down regulating α9-nAChR expression. In addition, our previous study, using a luciferase promoter activity experiment, demonstrated that α9-nAChR promoter activity was 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 demonstrated that treatment with TEIs (10 μg/mL) profoundly inhibited α9-nAChR proteins level when compared with EGCG-treatment alone in breast cancer cells. This study reveals the novel antitumor mechanisms of TEI, and these results may have significant applications for chemopreventive purposes in human breast cancer.