Journal Article

Characterizing properties of non-estrogenic substituted bisphenol analogs using high throughput microscopy and image analysis

Stossi, Fabio, Szafran, Adam T., Walker, Cheryl L., Mancini, Michael A., Mancini, Maureen G.

2017

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analogs / Analysis / Benzhydryl Compounds - pharmacology / Biocompatibility / Biological activity / Biology and Life Sciences / Biotechnology / Bisphenol A / Cell culture / Cell growth / Cell lines / Consumer products / Derivatives / Ecology and Environmental Sciences / Endocrine disruptors / Endocrine system / Estrogen / Estrogen Receptor alpha - metabolism / Estrogen Receptor beta - metabolism / Estrogen receptors / Estrogens / Estrogens, Non-Steroidal - chemistry / Estrogens, Non-Steroidal - pharmacology / HeLa Cells / High-Throughput Screening Assays - methods / Humans / Hydroquinone / Hydroquinones - pharmacology / Image analysis / Image processing / MCF-7 Cells / Microscopy / Molecular Structure / Phenols / Phenols - pharmacology / Physical Sciences / Prolactin / Properties (attributes) / Research and Analysis Methods / Rodents / Side effects / Transcription / Transcription, Genetic - drug effects / Xenoestrogens