Estrogen Receptor α Is Crucial in Zearalenone-Induced Invasion and Migration of Prostate Cancer Cells

Zearalenone (ZEA), a mycotoxin produced in the genus Fusarium, binds to estrogen receptors (ER) and is therefore regarded as an endocrine disruptor. ZEA has also been found to modulate the proliferation and apoptosis of prostate cancer cells in a dose-dependent manner. This study evaluates whether t...

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Main Authors: Karolina Kowalska, Dominika Ewa Habrowska-Górczyńska, Kinga Anna Urbanek, Kamila Domińska, Agnieszka Wanda Piastowska-Ciesielska
Format: Article
Language:English
Published: MDPI AG 2018-02-01
Series:Toxins
Subjects:
Online Access:http://www.mdpi.com/2072-6651/10/3/98
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author Karolina Kowalska
Dominika Ewa Habrowska-Górczyńska
Kinga Anna Urbanek
Kamila Domińska
Agnieszka Wanda Piastowska-Ciesielska
author_facet Karolina Kowalska
Dominika Ewa Habrowska-Górczyńska
Kinga Anna Urbanek
Kamila Domińska
Agnieszka Wanda Piastowska-Ciesielska
author_sort Karolina Kowalska
collection DOAJ
description Zearalenone (ZEA), a mycotoxin produced in the genus Fusarium, binds to estrogen receptors (ER) and is therefore regarded as an endocrine disruptor. ZEA has also been found to modulate the proliferation and apoptosis of prostate cancer cells in a dose-dependent manner. This study evaluates whether the effect of a low dose of ZEA (0.1 and 0.001 nM) on the invasion and migration of prostate cancer cell line PC3 is associated with ERs expression. The invasion and migration was evaluated by modified Boyden chamber assay, scratch assay, gelatin zymography, Real Time qPCR (RTqPCR) and Western blot. The involvement of ERs was evaluated with the selective ER antagonists: estrogen receptor α (ERα) antagonist 1,3-bis (4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy) phenol]-1H-pyrazole dihydrochloride (MPP) and estrogen receptor β (ERβ) antagonist 4-[2–phenyl-5,7–bis (trifluoromethyl) pyrazolo [1,5-a]-pyrimidin-3-yl] phenol (PHTPP). ZEA was found to modulate cell motility dependent on estrogen receptors, particularly ERα. Increased cell migration and invasion were associated with increased MMP-2 and MMP-9 activity as well as the up-regulation of the EMT-associated genes vimentin (VIM), zinc finger E-box-binding homeobox 1/2 (ZEB1/2) and transforming growth factor β 1 (TGFβ1). In conclusion, ZEA might modulate the invasiveness of prostate cancer cells dependently on ERα expression.
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spelling doaj.art-0e777cdfa92e4ac6942caf28c11ef0da2022-12-22T03:09:59ZengMDPI AGToxins2072-66512018-02-011039810.3390/toxins10030098toxins10030098Estrogen Receptor α Is Crucial in Zearalenone-Induced Invasion and Migration of Prostate Cancer CellsKarolina Kowalska0Dominika Ewa Habrowska-Górczyńska1Kinga Anna Urbanek2Kamila Domińska3Agnieszka Wanda Piastowska-Ciesielska4Laboratory of Cell Cultures and Genomic Analysis, Department of Comparative Endocrinology, Faculty of Biomedical Sciences and Postgraduate Education, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, PolandLaboratory of Cell Cultures and Genomic Analysis, Department of Comparative Endocrinology, Faculty of Biomedical Sciences and Postgraduate Education, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, PolandLaboratory of Cell Cultures and Genomic Analysis, Department of Comparative Endocrinology, Faculty of Biomedical Sciences and Postgraduate Education, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, PolandDepartment of Comparative Endocrinology, Faculty of Biomedical Sciences and Postgraduate Education, Medical University of Lodz, Zeligowskiego 7/9, 90-752, Lodz, PolandLaboratory of Cell Cultures and Genomic Analysis, Department of Comparative Endocrinology, Faculty of Biomedical Sciences and Postgraduate Education, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, PolandZearalenone (ZEA), a mycotoxin produced in the genus Fusarium, binds to estrogen receptors (ER) and is therefore regarded as an endocrine disruptor. ZEA has also been found to modulate the proliferation and apoptosis of prostate cancer cells in a dose-dependent manner. This study evaluates whether the effect of a low dose of ZEA (0.1 and 0.001 nM) on the invasion and migration of prostate cancer cell line PC3 is associated with ERs expression. The invasion and migration was evaluated by modified Boyden chamber assay, scratch assay, gelatin zymography, Real Time qPCR (RTqPCR) and Western blot. The involvement of ERs was evaluated with the selective ER antagonists: estrogen receptor α (ERα) antagonist 1,3-bis (4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy) phenol]-1H-pyrazole dihydrochloride (MPP) and estrogen receptor β (ERβ) antagonist 4-[2–phenyl-5,7–bis (trifluoromethyl) pyrazolo [1,5-a]-pyrimidin-3-yl] phenol (PHTPP). ZEA was found to modulate cell motility dependent on estrogen receptors, particularly ERα. Increased cell migration and invasion were associated with increased MMP-2 and MMP-9 activity as well as the up-regulation of the EMT-associated genes vimentin (VIM), zinc finger E-box-binding homeobox 1/2 (ZEB1/2) and transforming growth factor β 1 (TGFβ1). In conclusion, ZEA might modulate the invasiveness of prostate cancer cells dependently on ERα expression.http://www.mdpi.com/2072-6651/10/3/98zearalenonemycotoxinsestrogen receptors
spellingShingle Karolina Kowalska
Dominika Ewa Habrowska-Górczyńska
Kinga Anna Urbanek
Kamila Domińska
Agnieszka Wanda Piastowska-Ciesielska
Estrogen Receptor α Is Crucial in Zearalenone-Induced Invasion and Migration of Prostate Cancer Cells
Toxins
zearalenone
mycotoxins
estrogen receptors
title Estrogen Receptor α Is Crucial in Zearalenone-Induced Invasion and Migration of Prostate Cancer Cells
title_full Estrogen Receptor α Is Crucial in Zearalenone-Induced Invasion and Migration of Prostate Cancer Cells
title_fullStr Estrogen Receptor α Is Crucial in Zearalenone-Induced Invasion and Migration of Prostate Cancer Cells
title_full_unstemmed Estrogen Receptor α Is Crucial in Zearalenone-Induced Invasion and Migration of Prostate Cancer Cells
title_short Estrogen Receptor α Is Crucial in Zearalenone-Induced Invasion and Migration of Prostate Cancer Cells
title_sort estrogen receptor α is crucial in zearalenone induced invasion and migration of prostate cancer cells
topic zearalenone
mycotoxins
estrogen receptors
url http://www.mdpi.com/2072-6651/10/3/98
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AT kingaannaurbanek estrogenreceptoraiscrucialinzearalenoneinducedinvasionandmigrationofprostatecancercells
AT kamiladominska estrogenreceptoraiscrucialinzearalenoneinducedinvasionandmigrationofprostatecancercells
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