Zearalenone (ZEA), a mycotoxin produced in the genusFusarium, 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.
Toxins. 2018 Feb 28*** epublish ***
Karolina Kowalska, Dominika Ewa Habrowska-Górczyńska, Kinga Anna Urbanek, Kamila Domińska, Agnieszka Wanda Piastowska-Ciesielska
Laboratory 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, Poland. ., Laboratory 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, Poland. ., Laboratory 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, Poland. ., Department of Comparative Endocrinology, Faculty of Biomedical Sciences and Postgraduate Education, Medical University of Lodz, Zeligowskiego 7/9, 90-752, Lodz, Poland. ., Laboratory 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, Poland. .