Bisphenol A and nonylphenol have the potential to stimulate the migration of ovarian cancer cells by inducing epithelial-mesenchymal transition via an estrogen receptor dependent pathway.

Abstract

Epithelial-mesenchymal transition (EMT) is an important process appearing in embryo development and tumor migration or progression, which is influenced by 17β-estradiol (E2). Bisphenol A (BPA) and nonylphenol (NP) are suspected as endocrine disrupting chemicals (EDCs) because they can exert estrogenic properties. In this study, we examined whether E2, BPA, and NP can lead to the EMT process in BG-1 ovarian cancer cells expressing estrogen receptors (ERs). To confirm the effect of E2, BPA, and NP, BG-1 cells were cultured under treatment with E2, BPA, or NP, and the alteration of EMT markers such as vimentin was examined at mRNA levels by using real-time and reverse-transcription (RT)-PCR. The expressions of snail, slug, and vimentin were enhanced by the treatment of E2, BPA, or NP compared to a control (DMSO). In protein levels, vimentin protein was increased by E2 and two EDCs, while E-cadherin was decreased. In addition, the expression of snail protein was enhanced by the treatment of E2 and the two EDCs in comparison with that of the control. Since EMT response in cancer cells can affect metastasis, we also performed a scratch assay and Western blot assay to show the migration ability caused by E2, BPA, or NP. Consequently, E2, BPA, and NP enhanced the migration capability of BG-1 cells and increased the expression of MMP-9 protein. Furthermore, to examine whether EMT and migration of BG-1 cancer cells are induced by BPA or NP via the ER dependent pathway, we cotreated the cells with ER-antagonist, ICI 182,780, in the presence of E2, BPA, or NP. As a result, the expressions of E-cadherin, vimentin, snail, and slug were reversed following treatment with an ER antagonist. Moreover, we confirmed that ICI 182,780 reduced the migration ability of BPA and NP to the control level. Taken together, these results indicate that BPA and NP, the potential EDCs, may have the ability to influence ovarian cancer metastasis via regulating EMT markers and migration in ER-expressing BG-1 ovarian cancer cells.

• Authors: Ye-Seul Kim, Kyung-A Hwang, Sang-Hwan Hyun, Ki-Hoan Nam, Chang-Kyu Lee, Kyung-Chul Choi
• Journal: Chemical research in toxicology (Chem Res Toxicol) Vol. 28 Issue 4 Pg. 662-71 (Apr 20 2015) ISSN: 1520-5010 [Electronic] United States
• PMID: 25690688 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzhydryl Compounds
• Phenols
• RNA, Messenger
• Receptors, Estrogen
• SNAI1 protein, human
• Snail Family Transcription Factors
• Transcription Factors
• Vimentin
• nonylphenol
• Matrix Metalloproteinase 9
• bisphenol A

Topics

• Benzhydryl Compounds (toxicity)
• Cell Line, Tumor
• Epithelial-Mesenchymal Transition (drug effects)
• Female
• Humans
• Matrix Metalloproteinase 9 (genetics)
• Neoplasm Metastasis
• Ovarian Neoplasms (metabolism, pathology)
• Phenols (toxicity)
• RNA, Messenger (genetics)
• Receptors, Estrogen (physiology)
• Snail Family Transcription Factors
• Transcription Factors (genetics)
• Vimentin (genetics)