Tea polyphenol (−)-epigallocatechin-3-gallate inhibits nicotine- and estrogen-induced α9-nicotinic acetylcholine receptor upregulation in human breast cancer cells
✍ Scribed by 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
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 434 KB
- Volume
- 55
- Category
- Article
- ISSN
- 1613-4125
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✦ Synopsis
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.