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Bisphenol A alternatives can effectively substitute for estradiol in promoting cell growth through estrogen receptor alpha in human breast cancer cells

ABSTRACT: Plasticizers with estrogenic activity, such as bisphenol A (BPA), have been reported to have potential adverse health effects in humans, especially in fetal and infant stages. Due to mounting evidence and public pressure BPA is being phased out by the plastics manufacturing industry and is being replaced by other bisphenol variants in “BPA-free” products. We have compared estrogenic activity of 7 bisphenol analogues (BPA; bisphenol S, BPS; bisphenol F, BPF; bisphenol AP, BPAP; bisphenol AF, BPAF; bisphenol Z, BPZ; bisphenol B, BPB) in human breast cancer cell lines. We used microarrays to detail the alterations in gene expression profiles associated with MCF-7 cell line exposure to bisphenol A analogues

ORGANISM(S): Homo sapiens

PROVIDER: GSE85350 | GEO | 2017/03/03

SECONDARY ACCESSION(S): PRJNA338240

REPOSITORIES: GEO

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Project description:Bisphenols are used in the process of polymerization of polycarbonate plastics and epoxy resins, which have numerous applications in a variety of consumer products. Due to their hydrophobic properties, bisphenols can easily migrate out of plastic products especially into fatty foods. They have been found in brain, liver, adipose tissue and body fluids, illustrating their environmental prevalence. By increasing colonic inflammation in mice, disrupting the intestinal bacterial community structure and altering the microbial membrane transport system in zebrafish, bisphenols seem to interfere with the gut microbiome. The highly abundant human commensal bacterium Bacteroides thetaiotaomicron was exposed to bisphenols (Bisphenol A (BPA), Bisphenol F (BPF), Bisphenol S (BPS)), to examine the mode of action, in particular of BPF. All chemicals caused a concentration-dependent growth inhibition and the half-maximal effective concentration (EC50) corresponded to their individual logP values, a measure of their hydrophobicity. B. thetaiotaomicron exposed to BPF decreased membrane fluidity with increasing BPF concentrations. Physiological changes including an increase of acetate concentration were observed in cells treated with 0.57 mM BPF. On the proteome level, a higher abundance of several ATP synthase subunits and multidrug efflux pumps suggested an increased energy demand for adaptive mechanisms after BPF exposure. Defence mechanisms were also implicated by a pathway analysis, that identified a higher abundance of members of resistance pathways/strategies to cope with xenobiotics (i.e. antibiotics). Here, we present further insights into the mode of action of bisphenols in a human commensal gut bacterium regarding growth inhibition, and the physiological and functional state of the cell. These results, combined with microbiota-directed effects, could lead to a better understanding of host health disturbances and disease development based on xenobiotic uptake.

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Bisphenol A alternatives can effectively substitute for estradiol in promoting cell growth through estrogen receptor alpha in human breast cancer cells

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