Abstract

Bisphenol-A (BPA) has been considered as an endocrine disrupting chemical (EDC) because it can exert estrogenic properties. For bisphenol-S (BPS) and bisphenol-F (BPF) that are BPA analogs and substitutes, their risk to estrogen-dependent cancer has been reported rarely compared with the numerous cases of BPA. In this study, we examined whether BPA, BPS, and BPF can lead to the proliferation, migration, and epithelial mesenchymal transition (EMT) of MCF-7 clonal variant (MCF-7 CV) breast cancer cells expressing estrogen receptors (ERs). In a cell viability assay, BPA, BPS, and BPF significantly increased proliferation of MCF-7 CV cells compared to control (DMSO) as did 17β-estradiol (E2). In Western blotting assay, BPA, BPS, and BPF enhanced the protein expression of cell cycle progression genes such as cyclin D1 and E1. In addition, MCF-7 CV cells lost cell to cell contacts and acquired fibroblast-like morphology by the treatment of BPA, BPS, or BPF for 24 hours. In cell migration assay, BPA, BPS, and BPF accelerated the migration capability of MCF-7 CV cells as did E2. In relation with the EMT process, BPA, BPS, and BPF increased the protein expression ofN-cadherin, while they decreased the protein expression of E-cadherin. When BPA, BPS, and BPF were co-treated with ICI 182,780, an ER antagonist, proliferation effects were reversed, the expression of cyclin D1 and cyclin E1 was downregulated, and the altered cell migration and expression ofN-cadherin and E-cadherin by BPA, BPS, and BPF were restored to the control level. Thus, these results imply that BPS and BPF also have the risk of breast cancer progression as much as BPA in the induction of proliferation and migration of MCF-7 CV cells by regulating the protein expression of cell cycle-related genes and EMT markersvia the ER-dependent pathway.

Highlights

  • Endocrine-disrupting chemicals (EDCs) are exogen-Received 10 December 2016, Revised 19 January 2017, Accepted 02 May 2017, Epub 10 June 2017 CLC number: R6, Document code: A The authors reported no conflict of interests

  • To gain better understandings of cancer-related toxicity of BPS and BPF in comparison with BPA, which has been rarely discussed, we investigated whether they could affect cancer progression associated with proliferation, epithelial mesenchymal transition (EMT), and migration of estrogen-responsive breast cancer cells

  • This implies that BPA, BPS, and BPF can induce the proliferation of MCF-7 CV cells through estrogen receptors (ERs)-dependent pathway

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Summary

Introduction

Endocrine-disrupting chemicals (EDCs) are exogen-Received 10 December 2016, Revised 19 January 2017, Accepted 02 May 2017, Epub 10 June 2017 CLC number: R6, Document code: A The authors reported no conflict of interests. Doi:10.7555/JBR.31.20160162 such as the androgen receptor (AR) and estrogen receptor (ER) and thereby interrupt the functions of endogenous steroid hormones[3]. They can threaten health by generating reproductive and developmental disorders and cancer development and progression[4]. BPA is currently found in various plastic goods including electronic equipment, automobiles, children's toys, and water bottles. It is contained in the internal coatings of beverage and food cans and line water pipes[8]. BPA forced breast and prostate cells to be predisposed to cancer[14,15]

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