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...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2018-02-01
|
Series: | Toxins |
Subjects: | |
Online Access: | http://www.mdpi.com/2072-6651/10/3/98 |
_version_ | 1828740718362886144 |
---|---|
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. |
first_indexed | 2024-04-13T00:46:12Z |
format | Article |
id | doaj.art-0e777cdfa92e4ac6942caf28c11ef0da |
institution | Directory Open Access Journal |
issn | 2072-6651 |
language | English |
last_indexed | 2024-04-13T00:46:12Z |
publishDate | 2018-02-01 |
publisher | MDPI AG |
record_format | Article |
series | Toxins |
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 |
work_keys_str_mv | AT karolinakowalska estrogenreceptoraiscrucialinzearalenoneinducedinvasionandmigrationofprostatecancercells AT dominikaewahabrowskagorczynska estrogenreceptoraiscrucialinzearalenoneinducedinvasionandmigrationofprostatecancercells AT kingaannaurbanek estrogenreceptoraiscrucialinzearalenoneinducedinvasionandmigrationofprostatecancercells AT kamiladominska estrogenreceptoraiscrucialinzearalenoneinducedinvasionandmigrationofprostatecancercells AT agnieszkawandapiastowskaciesielska estrogenreceptoraiscrucialinzearalenoneinducedinvasionandmigrationofprostatecancercells |