Estrogen receptor-mediated actions of polyphenolic catechins in vivo and in vitro.

Abstract

Recent investigations have demonstrated that polyphenolic catechins inhibit breast cancer cell proliferation and tumor growth. However, the ER-mediated effects of the three predominant catechins (EGCG, ECG, and EGC) have not been extensively examined in vitro or in vivo. Therefore, EGCG, ECG, and EGC were examined for their ability to compete with [(3)H]-17beta-estradiol ([(3)H]-E(2)) for binding to ERalpha and ERbeta and to elicit reporter gene activity in MCF-7 human breast cancer cells transiently transfected with either chimeric ERalpha or ERbeta. EGCG and ECG displaced [(3)H]-E(2) from GST-hERalphadef (D, E, and F domains of human ERalpha fused to GST) or from full-length human ERbeta. Additionally, only EGCG elicited Gal4-hERalphadef and Gal4-mERbetadef-mediated reporter gene expression (EC(50) values: 28 and 19 micro M, respectively) in MCF-7 cells cotransfected with a Gal4-regulated luciferase reporter gene. In cotreatment experiments, EGCG (1-50 micro M) and ECG (1 micro M) decreased E(2)-induced (1 nM) ERbeta-mediated gene expression 35-50%. In vivo, no catechin induced estrogenic responses (uterine weight or uterine peroxidase activity) in immature C57BL/6 mice. However, when mice were cotreated with E(2) (10 micro g/kg/day, 3 days) and either EGCG (30 and 50 mg/kg/day, 3 days) or ECG (50 mg/kg/day, 3 days), uterine peroxidase activity was increased 2.3-fold above that elicited by E(2) alone. In conclusion, EGCG and ECG bind to ERalpha and ERbeta, but only EGCG elicited ER-mediated gene expression in vitro. However, both of these compounds moderately increased E(2)-inducible responses in vivo.