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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MDPI AG
2021-10-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/13/11/766 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:00:46Z |
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| id | doaj.art-0bbbb8ae8e9340e39ca4b1e0600631ed |
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| language | English |
| last_indexed | 2024-03-10T05:00:46Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-0bbbb8ae8e9340e39ca4b1e0600631ed2023-11-23T01:48:44ZengMDPI AGToxins2072-66512021-10-01131176610.3390/toxins13110766Estrogen Receptor β Participates in Alternariol-Induced Oxidative Stress in Normal Prostate Epithelial CellsKarolina Kowalska0Marta Justyna Kozieł1Kinga Anna Urbanek2Dominika Ewa Habrowska-Górczyńska3Kamila Domińska4Agnieszka Wanda Piastowska-Ciesielska5Department of Cell Cultures and Genomic Analysis, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, PolandDepartment of Cell Cultures and Genomic Analysis, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, PolandDepartment of Cell Cultures and Genomic Analysis, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, PolandDepartment of Cell Cultures and Genomic Analysis, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, PolandDepartment of Comparative Endocrinology, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, PolandDepartment of Cell Cultures and Genomic Analysis, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, Poland<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.https://www.mdpi.com/2072-6651/13/11/766alternariolmycotoxinprostateoxidative stressDNA damage |
| spellingShingle | 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 Toxins alternariol mycotoxin prostate oxidative stress DNA damage |
| title | 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_short | 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 |
| topic | alternariol mycotoxin prostate oxidative stress DNA damage |
| url | https://www.mdpi.com/2072-6651/13/11/766 |
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