ERβ and NFκB-Modulators of Zearalenone-Induced Oxidative Stress in Human Prostate Cancer Cells.

Karolina Kowalska,Dominika Ewa Habrowska-Górczyńska,Agnieszka Wanda Piastowska-Ciesielska,Kamila Domińska,Kinga Anna Urbanek

doi:10.3390/toxins12030199

Karolina Kowalska, Dominika Ewa Habrowska-Górczyńska + Show 3 more

Open Access

https://doi.org/10.3390/toxins12030199

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Journal: Toxins	Publication Date: Mar 22, 2020
Citations: 13	License type: CC BY 4.0

Affiliation: Medical University of Lodz

Abstract

Nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) is commonly expressed in prostate cancer (PCa) cells and is associated with increased proliferation, metastases and androgen independence. Zearalenone (ZEA) is one of the most common mycotoxins contaminating food, which might mimic estrogens and bind to estrogen receptors (ERs). The ratio of androgens to estrogens in men decreases physiologically with age, and is believed to participate in prostate carcinogenesis. In this study, we evaluated the role of NFκB and ERβ in the induction of oxidative stress in human PCa cells by ZEA. As observed, ZEA at a dose of 30 µM induces oxidative stress in PCa cells associated with DNA damage and G2/M cell cycle arrest. We also observed that the inhibition of ERβ and NFΚB via specific inhibitors (PHTPP and BAY 117082) significantly increased ZEA-induced oxidative stress, although the mechanism seems to be different for androgen-dependent and androgen-independent cells. Based on our findings, it is possible that the activation of ERβ and NFΚB in PCa might protect cancer cells from ZEA-induced oxidative stress. We therefore shed new light on the mechanism of ZEA toxicity in human cells.

Highlights

Oxidative stress in cancer cells plays a dual role: the generation of reactive oxygen species (ROS) in cells increases the proliferation and migration of cells and participates in the initiation and progression of prostate cancer (PCa) [1], but on the other hand, excessive ROS production induces DNA damage and triggers apoptosis [2]
Pathways, we evaluated whether ZEA itself and in combination with PHTPP and BAY decreases the viability of PCa cells
Our results showed that active estrogen receptor β (ERβ) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB) might protect PCa cells from ZEA-induced oxidative stress, but this statement needs to be confirmed in further studies

Summary

Introduction

Oxidative stress in cancer cells plays a dual role: the generation of reactive oxygen species (ROS) in cells increases the proliferation and migration of cells and participates in the initiation and progression of PCa [1], but on the other hand, excessive ROS production induces DNA damage and triggers apoptosis [2]. Nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB) signaling pathway is believed to be a link between inflammation and cancer, due to the induction of proliferation, blocking apoptosis in cells and maintaining angiogenesis [3], and the induction of oxidative stress with hypoxia inducible factor 1 alpha (HIF-1α) and estrogen receptor β (ERβ) [4]. ZEA is considered noncancerogenic to humans; research has reported that it might have a carcinogenic effect via the induction of proliferation, migration and invasion of cells [8]. ZEA is reported to modulate the activation of inflammasome via p65 in INS-1 cells [11]; a direct association between ZEA and NFKB has not been found yet, especially in the case of cancer cells, where the activation of NFKB plays a role

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