Estrogen modulation properties of mangiferin and quercetin and the mangiferin metabolite norathyriol

Mango fruit contain many bioactive compounds, some of which are transcription factor regulators. Estrogen receptor alpha (ER alpha) and beta (ER beta) are two regulators of gene transcription that are important in a variety of physiological processes and also in diseases including breast cancer. We examined the ability of the mango constituents quercetin, mangiferin, and the aglycone form of mangiferin, norathyriol, to activate both isoforms of the estrogen receptor. Quercetin and norathyriol decreased the viability of MCF-7 breast cancer cells whereas mangiferin had no effect on MCF-7 cells. We also determined that quercetin and mangiferin selectively activated ER alpha whereas norathyriol activated both ER alpha and ER beta. Despite quercetin, mangiferin and norathyriol having similar polyphenolic structural motifs, only norathyriol activated ER beta, showing that bioactive agents in mangoes have very specific biological effects. Such specificity may be important given the often-opposing roles of ER alpha and ER beta in breast cancer proliferation and other cellular processes