Butyl octyl phthalate interacts with estrogen receptor α in MCF‑7 breast cancer cells to promote cancer development

Böckers,Madeleine; Paul,Norbert W.; Efferth,Thomas

doi:10.3892/wasj.2021.92

Butyl octyl phthalate interacts with estrogen receptor α in MCF‑7 breast cancer cells to promote cancer development

Authors:
- Madeleine Böckers
- Norbert W. Paul
- Thomas Efferth
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Affiliations: Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, D-55128 Mainz, Germany, Institute for History, Theory and Ethics of Medicine, Johannes Gutenberg University Medical Center, D-55131 Mainz, Germany
Published online on: February 12, 2021 https://doi.org/10.3892/wasj.2021.92
Article Number: 21
Copyright: © Böckers et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Environmental pollution with microplastics and in particular, the leaching of plasticizers is increasingly regarded with concern. The uptake of microplastics by marine animals may lead to plasticizers entering the food chain, which can affect human health. Phthalate compounds are considered to act as endocrine disruptors. The present study aimed to analyze the effects of the three phthalates, benzyl butyl phthalate (BBP), butyl cyclohexyl phthalate (BCP) and butyl octyl phthalate (BOP), on the MCF‑7 human breast cancer cell line. For this purpose, molecular docking and microscale thermophoresis were applied, and estrogen receptor α (ERα) activation was measured in ESR1‑overexpressing 293 cells. BBP, BCP and BOP bound in silico and in vitro to ERα and activated the receptor. In addition, next‑generation sequencing was applied and 15 differentially expressed genes were found following treatment of the MCF‑7 cells with BOP: CYP1A1, DDIT4, KLHL24, SLC7A11, CEACAM5, STC2, SLC7A5 and IER3 were upregulated, while FKBP4, TFAP2C, CDK1, CCNA2, PGR, SFPQ, and ADORA1 were downregulated. The gene expression pattern was associated with interference in the cell cycle, and an increased tumorigenesis, proliferation, metastasis and poorer survival of cancer cells. In total, the findings of the present study reveal an endocrine disruptive potential effect of BOP on MCF‑7 breast cancer cells and demonstrate the interaction of BBP, BCP and BOP with ERα in vitro.

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