Lani
01-24-2008, 08:11 AM
ABSTRACT: Epigallocatechin-3-gallate downregulates estrogen receptor alpha function in MCF-7 breast carcinoma cells
[Cancer Detection & Prevention]
Background: (-)-Epigallocatechin-3-gallate (EGCG) is the most active catechin 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-β-estradiol for binding to estrogen receptor alpha (ERα), we asked whether EGCG could regulate ERα action.
Methods: We used MCF-7, a breast carcinoma cell line having a high level of ERα expression. The cells were treated with various EGCG concentrations and cell viability was evaluated by MTT assay. ERα and pS2 expression were analyzed by RT-PCR after RNA extraction. To better define EGCG action in relation to ERα, we studied EGCG cytotoxicity on MCF-7 resistant to tamoxifen (MCF-7tam), MCF-7 treated with 10-7 M ICI 182,780 for 8 days and on MDA-MB-231, a cell line that lacked ERα by flow cytometry (FCM).
Results: Both ERα 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 h, indicating ERα alteration. EGCG cytotoxicity was lower when ERα was not present (MDA-MB-231) or inactivated (by tamoxifen or ICI 182,780).
Conclusions: Functionally active ERα may have a role in EGCG cytotoxicity, increasing the sensitivity to the drug. As higher EGCG concentrations also killed cells resistant to tamoxifen or treated by 10-7 M ICI 182,780, EGCG ought to be better investigated in breast carcinoma cells treated with drugs targeted to steroid receptors, as a potential complement of therapy.
[Cancer Detection & Prevention]
Background: (-)-Epigallocatechin-3-gallate (EGCG) is the most active catechin 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-β-estradiol for binding to estrogen receptor alpha (ERα), we asked whether EGCG could regulate ERα action.
Methods: We used MCF-7, a breast carcinoma cell line having a high level of ERα expression. The cells were treated with various EGCG concentrations and cell viability was evaluated by MTT assay. ERα and pS2 expression were analyzed by RT-PCR after RNA extraction. To better define EGCG action in relation to ERα, we studied EGCG cytotoxicity on MCF-7 resistant to tamoxifen (MCF-7tam), MCF-7 treated with 10-7 M ICI 182,780 for 8 days and on MDA-MB-231, a cell line that lacked ERα by flow cytometry (FCM).
Results: Both ERα 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 h, indicating ERα alteration. EGCG cytotoxicity was lower when ERα was not present (MDA-MB-231) or inactivated (by tamoxifen or ICI 182,780).
Conclusions: Functionally active ERα may have a role in EGCG cytotoxicity, increasing the sensitivity to the drug. As higher EGCG concentrations also killed cells resistant to tamoxifen or treated by 10-7 M ICI 182,780, EGCG ought to be better investigated in breast carcinoma cells treated with drugs targeted to steroid receptors, as a potential complement of therapy.