Estrogen Receptor-Mediated Actions of Polyphenolic Catechins in Vivo and in Vitro

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 [3H]-17β-estradiol ([3H]-E2) for binding to ERα and ERβ and to elicit reporter gene activity in MCF-7 human breast cancer cells transiently transfected with either chimeric ERα or ERβ. EGCG and ECG displaced [3H]-E2 from GST-hERαdef (D, E, and F domains of human ERα fused to GST) or from full-length human ERβ. Additionally, only EGCG elicited Gal4-hERαdef and Gal4-mERβdef-mediated reporter gene expression (EC50 values: 28 and 19 μM, respectively) in MCF-7 cells cotransfected with a Gal4-regulated luciferase reporter gene. In cotreatment experiments, EGCG (1–50 μM) and ECG (1 μM) decreased E2-induced (1 nM) ERβ-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 E2 (10 μg/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 E2 alone. In conclusion, EGCG and ECG bind to ERα and ERβ, but only EGCG elicited ER-mediated gene expression in vitro. However, both of these compounds moderately increased E2-inducible responses in vivo.