Estrogen receptor α mediates alternariol-induced apoptosis and modulation of the invasiveness of ovarian cancer cells

Marta Justyna Kozieł; Dominika Ewa Habrowska-Górczyńska; Kinga Anna Urbanek; Kamila Domińska; Agnieszka Wanda Piastowska-Ciesielska; Karolina Kowalska

doi:10.1016/j.toxlet.2023.09.001

Estrogen receptor α mediates alternariol-induced apoptosis and modulation of the invasiveness of ovarian cancer cells

Toxicol Lett. 2023 Sep 1:386:9-19. doi: 10.1016/j.toxlet.2023.09.001. Epub 2023 Sep 6.

Authors

Marta Justyna Kozieł¹, Dominika Ewa Habrowska-Górczyńska², Kinga Anna Urbanek², Kamila Domińska³, Agnieszka Wanda Piastowska-Ciesielska¹, Karolina Kowalska⁴

Affiliations

¹ Medical University of Lodz, Department of Cell Cultures and Genomic Analysis, Lodz, Poland; Medical University of Lodz, BRaIn Laboratories, Lodz, Poland.
² Medical University of Lodz, Department of Cell Cultures and Genomic Analysis, Lodz, Poland.
³ Medical University of Lodz, Department of Comparative Endocrinology, Lodz, Poland.
⁴ Medical University of Lodz, Department of Cell Cultures and Genomic Analysis, Lodz, Poland. Electronic address: karolina.kowalska1@umed.lodz.pl.

PMID: 37683805
DOI: 10.1016/j.toxlet.2023.09.001

Abstract

Mycotoxins are secondary metabolites of fungi that may affect both human and animal health. Some of them possess estrogenic activity, due to direct binding to estrogen receptors (ERs) and hence disturb the hormonal balance of the organism. Alternariol (AOH) was previously reported as genotoxic, estrogenic and immunomodulatory agent. However, detailed mechanism of its action has not been fully elucidated. Estrogen receptor α (ERα) was previously reported to modulate the proliferation and invasiveness of ovarian cancer cells. Thus, we decided to verify whether estrogenic-like mycotoxin may affect ovarian cancer cells via ERα. The results showed that AOH induces apoptosis and oxidative stress and that these effects are partially modulated by ERα. Moreover, AOH decreases the invasion and migration of ovarian cancer cells and promotes changes in the expression of genes and proteins that are associated with the invasiveness of cancer i.e. MMP9, SNAIL1/2, ZEB1/2, VIM, CDH1 and CDH2. In conclusion, we postulate that AOH might significantly affect the viability and invasiveness of ovarian cancer cells via modulation of ERα and therefore possibly act as an endocrine disruptive agent in ovarian cancer cells.

Keywords: Alternariol; Motility; Mycotoxins; Ovarian cancer; Oxidative stress.