(-)-Epigallocatechin-3-gallate down regulates estrogen receptor alpha function in MCF-7 breast carcinoma cells

ABSTRACT Background: EGCG is the most active principle present in green tea, demonstrated to have chemopreventive action and to kill cancer cells selectively. As a previous study found that catechins could compete with 17-alpha-estradiol for binding to estrogen receptors alpha (ER), we asked whether EGCG could regulate ER action. Methods: We used MCF-7, a breast carcinoma cell line having great ER expression. The cells were treated with various EGCG concentrations and cell viability evaluated by MTT assay. ER and pS2 expression were analyzed by RT-PCR after RNA extraction. To better define EGCG action in relation to ER, we studied EGCG cytotoxicity on MCF-7 resistant to tamoxifen (MCF-7tam), MCF-7 treated with 10-7 M ICI 780,181 for 8 days, and MDA-MB-231, a cell line that lacked ER, by Flow Cytometry (FCM). Results: Both ER and pS2 mRNA were expressed in samples treated with low EGCG concentration (30 µg/ml). At this concentration, no cell change was detectable. In contrast, pS2 expression was lost in samples treated with 100 µg/ml EGCG for 24 hours, indicating ER functional inactivation. EGCG cytotoxicity was lower when ER was not present (MDA-MB-231) or inactivated (by tamoxifen or ICI 780,181). Conclusions: Functionally active ER may have a role in EGCG cytotoxicity, increasing the sensitivity to the drug. As greater EGCG concentrations could also kill cells resistant to tamoxifen or treated by 10-7 M ICI 780,181, EGCG ought to be better investigated in breast carcinoma cells treated with drugs targeted to steroid receptors as a potential complement of therapy.