Mechanisms enforcing the estrogen receptor beta selectivity of botanical estrogens.
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Jiang Y, Gong P, Madak-Erdogan Z, Martin T, Jeyakumar M, Carlson K, Khan I, Smillie TJ, Chittiboyina AG, Rotte SC, Helferich WG, Katzenellenbogen JA, Katzenellenbogen BS
Mechanisms enforcing the estrogen receptor beta selectivity of botanical estrogens.
FASEB J. 2013 Nov;27(11):4406-18. doi: 10.1096/fj.13-234617. Epub 2013 Jul 23.
- PubMed ID
- 23882126 [ View in PubMed]
- Abstract
Because little is known about the actions of botanical estrogens (BEs), widely consumed by menopausal women, we investigated the mechanistic and cellular activities of some major BEs. We examined the interactions of genistein, daidzein, equol, and liquiritigenin with estrogen receptors ERalpha and ERbeta, with key coregulators (SRC3 and RIP140) and chromatin binding sites, and the regulation of gene expression and proliferation in MCF-7 breast cancer cells containing ERalpha and/or ERbeta. Unlike the endogenous estrogen, estradiol (E2), BEs preferentially bind to ERbeta, but their ERbeta-potency selectivity in gene stimulation (340- to 830-fold vs. E2) is enhanced at several levels (coregulator recruitment, chromatin binding); nevertheless, at high (0.1 or 1 muM) concentrations, BEs also fully activate ERalpha. Because ERalpha drives breast cancer cell proliferation and ERbeta dampens this, the relative levels of these two ERs in target cells and the BE dose greatly affect gene expression and proliferative response and will be crucial determinants of the potential benefits vs. risks of BEs. Our findings reveal key and novel mechanistic differences in the estrogenic activities of BEs vs. E2, with BEs displaying patterns of activity distinctly different from those seen with E2 and provide valuable information to inform future studies.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Estradiol Estrogen receptor beta Protein Humans YesAgonistDetails