Title: Characterizing properties of non-estrogenic substituted bisphenol analogs using high throughput microscopy and image analysis.
Authors: Szafran, Adam T; Stossi, Fabio; Mancini, Maureen G; Walker, Cheryl L; Mancini, Michael A
Published In PLoS One, (2017)
Abstract: Animal studies have linked the estrogenic properties of bisphenol A (BPA) to adverse effects on the endocrine system. Because of concerns for similar effects in humans, there is a desire to replace BPA in consumer products, and a search for BPA replacements that lack endocrine-disrupting bioactivity is ongoing. We used multiple cell-based models, including an established multi-parametric, high throughput microscopy-based platform that incorporates engineered HeLa cell lines with visible ERα- or ERβ-regulated transcription loci, to discriminate the estrogen-like and androgen-like properties of previously uncharacterized substituted bisphenol derivatives and hydroquinone. As expected, BPA induced 70-80% of the estrogen-like activity via ERα and ERβ compared to E2 in the HeLa prolactin array cell line. 2,2' BPA, Bisguaiacol F, CHDM 4-hydroxybuyl acrylate, hydroquinone, and TM modified variants of BPF showed very limited estrogen-like or androgen-like activity (< 10% of that observed with the control compounds). Interestingly, TM-BFP and CHDM 4-hydroxybuyl acrylate, but not their derivatives, demonstrated evidence of anti-estrogenic and anti-androgenic activity. Our findings indicate that Bisguaiacol F, TM-BFP-ER and TM-BPF-DGE demonstrate low potential for affecting estrogenic or androgenic endocrine activity. This suggest that the tested compounds could be suitable commercially viable alternatives to BPA.
PubMed ID: 28704378
MeSH Terms: Benzhydryl Compounds/pharmacology; Estrogen Receptor alpha/metabolism; Estrogen Receptor beta/metabolism; Estrogens, Non-Steroidal/chemistry; Estrogens, Non-Steroidal/pharmacology*; HeLa Cells; High-Throughput Screening Assays/methods*; Humans; Hydroquinones/pharmacology; MCF-7 Cells; Microscopy; Molecular Structure; Phenols/pharmacology; Transcription, Genetic/drug effects*