Characterization of Flavonoids With Potent and Subtype-Selective Actions on Estrogen Receptors Alpha and Beta

Authors

Michael J Bolt
Jessica Oceguera
Pankaj K Singh
Kazem Safari
Derek H Abbott
Kaley A Neugebauer
Maureen G Mancini
Daniel A Gorelick
Fabio Stossi
Michael A Mancini

Publication Date

3-15-2024

Journal

iScience

DOI

10.1016/j.isci.2024.109275

PMID

38469564

PMCID

PMC10926205

PubMedCentral® Posted Date

2-20-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Biological sciences, Endocrinology, endocrine regulation, Phytochemistry, Biological sciences, Endocrinology, endocrine regulation, Phytochemistry

Abstract

The initial step in estrogen-regulated transcription is the binding of a ligand to its cognate receptors, named estrogen receptors (ERα and ERβ). Phytochemicals present in foods and environment can compete with endogenous hormones to alter physiological responses. We screened 224 flavonoids in our engineered biosensor ERα and ERβ PRL-array cell lines to characterize their activity on several steps of the estrogen signaling pathway. We identified 83 and 96 flavonoids that can activate ERα or ERβ, respectively. While most act on both receptors, many appear to be subtype-selective, including potent flavonoids that activate ER at sub-micromolar concentrations. We employed an orthogonal assay using a transgenic zebrafish

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