Abstract |
Plasticizers released from microplastic are increasingly viewed with concern. While adverse health effects induced by bisphenol A and its analogues on marine animals are well documented in the literature, the endocrine potential of bisphenolic compounds on human health remains elusive. We applied next generation sequencing (NGS) with the estrogen receptor α (ERα) positive human breast cancer cell line MCF-7 treated with 17-β-estradiol (E2), bisphenol A (BPA), bisphenol B (BPB), bisphenol Z (BPZ) and tetramethyl bisphenol A (4MeBPA). We used molecular docking, microscale thermophoresis, ERα activation assay, and cell cycle experiments on MCF-7 and ERα overexpressing HEK293 cells to verify the impact of the compounds on ERα. 14 genes were found upregulated (ADORA1, DDIT4, CELSR2, FOSL2, JUN, HSPA13, IER3, IGF1R, PGR, RUNX2, SLC7A11, SLC7A2, SLC7A5, STC2) and 3 genes were downregulated (BCAS3, PHF19, PRKCD) in almost all samples. These genes are associated with cell growth, invasion, migration, apoptosis and cancer development. We further confirmed the binding, activation and proliferative effect of BPA, BPB, BPZ, and 4MeBPA on ERα. We provide evidence for the endocrine potential of bisphenolic compounds and give insights into their molecular effects in MCF-7 cells.
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Authors | Madeleine Böckers, Norbert W Paul, Thomas Efferth |
Journal | Toxicology and applied pharmacology
(Toxicol Appl Pharmacol)
Vol. 399
Pg. 115030
(07 15 2020)
ISSN: 1096-0333 [Electronic] United States |
PMID | 32387340
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 Elsevier Inc. All rights reserved. |
Chemical References |
- Benzhydryl Compounds
- ESR1 protein, human
- Endocrine Disruptors
- Estrogen Receptor alpha
- Estrogens
- Phenols
- Plasticizers
- bisphenol B
- Estradiol
- bisphenol A
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Topics |
- Benzhydryl Compounds
(pharmacology)
- Breast Neoplasms
(genetics)
- Cell Line
- Cell Line, Tumor
- Cell Proliferation
(drug effects, genetics)
- Down-Regulation
(drug effects, genetics)
- Endocrine Disruptors
(pharmacology)
- Estradiol
(genetics)
- Estrogen Receptor alpha
(genetics)
- Estrogens
(genetics)
- Female
- Gene Expression
(drug effects)
- HEK293 Cells
- Humans
- MCF-7 Cells
- Phenols
(pharmacology)
- Plasticizers
(pharmacology)
- Signal Transduction
(drug effects, genetics)
- Up-Regulation
(drug effects, genetics)
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