Estrogen Receptor β Participates in Alternariol-Induced Oxidative Stress in Normal Prostate Epithelial Cells

<i>Alternaria</i> toxins are considered as emerging mycotoxins, however their toxicity has not been fully evaluated in humans. Alternariol (AOH), the most prevalent <i>Alternaria</i> mycotoxin, was previously reported to be genotoxic and to affect hormonal balance in cells; h...

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Autores principales:	Karolina Kowalska, Marta Justyna Kozieł, Kinga Anna Urbanek, Dominika Ewa Habrowska-Górczyńska, Kamila Domińska, Agnieszka Wanda Piastowska-Ciesielska
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	alternariol mycotoxin prostate oxidative stress DNA damage Medicine R
Acceso en línea:	https://doaj.org/article/0bbbb8ae8e9340e39ca4b1e0600631ed
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id	oai:doaj.org-article:0bbbb8ae8e9340e39ca4b1e0600631ed
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spelling	oai:doaj.org-article:0bbbb8ae8e9340e39ca4b1e0600631ed2021-11-25T19:08:40ZEstrogen Receptor β Participates in Alternariol-Induced Oxidative Stress in Normal Prostate Epithelial Cells10.3390/toxins131107662072-6651https://doaj.org/article/0bbbb8ae8e9340e39ca4b1e0600631ed2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6651/13/11/766https://doaj.org/toc/2072-6651<i>Alternaria</i> toxins are considered as emerging mycotoxins, however their toxicity has not been fully evaluated in humans. Alternariol (AOH), the most prevalent <i>Alternaria</i> mycotoxin, was previously reported to be genotoxic and to affect hormonal balance in cells; however, its direct molecular mechanism is not known. The imbalance in androgen/estrogen ratio as well as chronic inflammation are postulated as factors in prostate diseases. The environmental agents affecting the hormonal balance might participate in prostate carcinogenesis. Thus, this study evaluated the effect of two doses of AOH on prostate epithelial cells. We observed that AOH in a dose of 10 µM induces oxidative stress, DNA damage and cell cycle arrest and that this effect is partially mediated by estrogen receptor β (ERβ) whereas the lower tested dose of AOH (0.1 µM) induces only oxidative stress in cells. The modulation of nuclear erythroid-related factor 2 (Nrf2) was observed in response to the higher dose of AOH. The use of selective estrogen receptor β (ERβ) inhibitor PHTPP revealed that AOH-induced oxidative stress in both tested doses is partially dependent on activation of ERβ, but lack of its activation did not protect cells against AOH-induced ROS production or DNA-damaging effect in case of higher dose of AOH (10 µM). Taken together, this is the first study reporting that AOH might affect basic processes in normal prostate epithelial cells associated with benign and malignant changes in prostate tissue.Karolina KowalskaMarta Justyna KoziełKinga Anna UrbanekDominika Ewa Habrowska-GórczyńskaKamila DomińskaAgnieszka Wanda Piastowska-CiesielskaMDPI AGarticlealternariolmycotoxinprostateoxidative stressDNA damageMedicineRENToxins, Vol 13, Iss 766, p 766 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	alternariol mycotoxin prostate oxidative stress DNA damage Medicine R
spellingShingle	alternariol mycotoxin prostate oxidative stress DNA damage Medicine R Karolina Kowalska Marta Justyna Kozieł Kinga Anna Urbanek Dominika Ewa Habrowska-Górczyńska Kamila Domińska Agnieszka Wanda Piastowska-Ciesielska Estrogen Receptor β Participates in Alternariol-Induced Oxidative Stress in Normal Prostate Epithelial Cells
description	<i>Alternaria</i> toxins are considered as emerging mycotoxins, however their toxicity has not been fully evaluated in humans. Alternariol (AOH), the most prevalent <i>Alternaria</i> mycotoxin, was previously reported to be genotoxic and to affect hormonal balance in cells; however, its direct molecular mechanism is not known. The imbalance in androgen/estrogen ratio as well as chronic inflammation are postulated as factors in prostate diseases. The environmental agents affecting the hormonal balance might participate in prostate carcinogenesis. Thus, this study evaluated the effect of two doses of AOH on prostate epithelial cells. We observed that AOH in a dose of 10 µM induces oxidative stress, DNA damage and cell cycle arrest and that this effect is partially mediated by estrogen receptor β (ERβ) whereas the lower tested dose of AOH (0.1 µM) induces only oxidative stress in cells. The modulation of nuclear erythroid-related factor 2 (Nrf2) was observed in response to the higher dose of AOH. The use of selective estrogen receptor β (ERβ) inhibitor PHTPP revealed that AOH-induced oxidative stress in both tested doses is partially dependent on activation of ERβ, but lack of its activation did not protect cells against AOH-induced ROS production or DNA-damaging effect in case of higher dose of AOH (10 µM). Taken together, this is the first study reporting that AOH might affect basic processes in normal prostate epithelial cells associated with benign and malignant changes in prostate tissue.
format	article
author	Karolina Kowalska Marta Justyna Kozieł Kinga Anna Urbanek Dominika Ewa Habrowska-Górczyńska Kamila Domińska Agnieszka Wanda Piastowska-Ciesielska
author_facet	Karolina Kowalska Marta Justyna Kozieł Kinga Anna Urbanek Dominika Ewa Habrowska-Górczyńska Kamila Domińska Agnieszka Wanda Piastowska-Ciesielska
author_sort	Karolina Kowalska
title	Estrogen Receptor β Participates in Alternariol-Induced Oxidative Stress in Normal Prostate Epithelial Cells
title_short	Estrogen Receptor β Participates in Alternariol-Induced Oxidative Stress in Normal Prostate Epithelial Cells
title_full	Estrogen Receptor β Participates in Alternariol-Induced Oxidative Stress in Normal Prostate Epithelial Cells
title_fullStr	Estrogen Receptor β Participates in Alternariol-Induced Oxidative Stress in Normal Prostate Epithelial Cells
title_full_unstemmed	Estrogen Receptor β Participates in Alternariol-Induced Oxidative Stress in Normal Prostate Epithelial Cells
title_sort	estrogen receptor β participates in alternariol-induced oxidative stress in normal prostate epithelial cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0bbbb8ae8e9340e39ca4b1e0600631ed
work_keys_str_mv	AT karolinakowalska estrogenreceptorbparticipatesinalternariolinducedoxidativestressinnormalprostateepithelialcells AT martajustynakozieł estrogenreceptorbparticipatesinalternariolinducedoxidativestressinnormalprostateepithelialcells AT kingaannaurbanek estrogenreceptorbparticipatesinalternariolinducedoxidativestressinnormalprostateepithelialcells AT dominikaewahabrowskagorczynska estrogenreceptorbparticipatesinalternariolinducedoxidativestressinnormalprostateepithelialcells AT kamiladominska estrogenreceptorbparticipatesinalternariolinducedoxidativestressinnormalprostateepithelialcells AT agnieszkawandapiastowskaciesielska estrogenreceptorbparticipatesinalternariolinducedoxidativestressinnormalprostateepithelialcells
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Estrogen Receptor β Participates in Alternariol-Induced Oxidative Stress in Normal Prostate Epithelial Cells

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