Regulation of the Estrogen Receptor via Catechin Polyphenols from Green Tea

It has long been suggested that green tea could aid in preventing breast cancer. Green tea is rich in catechin polyphenols that have been associated with bioactive properties, such as anti-proliferative effects on antiestrogen resistant breast cancer cells. There is currently no consensus mechanism for how catechins work. Proposed mechanisms include both estrogen receptor dependent and independent pathways. Studies in the Weatherman laboratory conclude that green tea catechin polyphenols, particularly catechin gallates, exhibit weak estrogenic effects on estrogen receptor(ER)-mediated transcription. The catechins tested were (-)-Epicatechin gallate, (-)-Gallocatechin gallate, (-)-Epigallocatechin, and (-)-Gallocatechin. This research determined the antiestrogen strength of these catechins relative to prominent antiestrogens, and tested them in antiestrogen sensitive and resistant cell lines to determine catechin polyphenol behavior as agonistic or antagonistic. This was accomplished via fluorescent polarization binding assay and luciferase assay. The FP binding assay results showed that catechins do indeed demonstrate successful binding to ER at high concentration doses, but they are weaker than prominent antiestrogens. The luciferase assay data demonstrated that catechins are able to stimulate ER-mediated transcription, but at levels lower than those observed with estradiol. However, the extent of catechin ER-mediated transcription activation does not seem to correlate with binding affinity. This suggests a more complicated mechanism to be analyzed in the future. Further studies will also dissect whether these catechin polyphenols, particularly the catechin gallates, are low potency full agonists or high potency partial agonists. Comparative studies regarding ER alpha and ER beta behavior will be examined.