Zearalenone (ZEA), a mycotoxin produced in the genus Fusarium, 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.

Nuclear factor erythroid 2-like 2 (Nrf2) is a transcription factor participating in response to cellular oxidative stress to maintain the redox balance. Generation of reactive oxygen species (ROS) and, in consequence, oxidative stress, are physiological as well as pathological processes which take place in almost all types of cells. Nrf2, in response to oxidative stress, activates expression and production of antioxidant enzymes to remove free radicals. However, the role of Nrf2 seems to be more sophisticated and its increased expression observed in cancer cells allows to draw a conclusion that its role is tissue—and condition—dependent. Interestingly, Nrf2 might also play a crucial role in response to environmental factors like mycotoxins. Thus, the aim of the study is to review the role of Nrf2 in cells exposed to most common mycotoxins to check if the Nrf2 signaling pathway serves as the main response element to mycotoxin-induced oxidative stress in human and animal cells and if it can be a target of detoxifying agents.

Forkhead box O3 (FOXO3a) is a member of a subfamily of forkhead transcription factors involved in the basic processes within a cell, including proliferation, apoptosis, cell cycle regulation, and DNA damage. As a transcription factor, FOXO3a is involved in the response to cellular stress, UV radiation, or oxidative stress. Its regulation is based on the modification of proteins as well as regulation by other proteins, e.g., growth factors. FOXO3a is commonly deregulated in cancer cells, and its inactivation is associated with initiation and progression of tumorigenesis, suggesting its role as a tumor suppressor; however, its role is still disputed and seems to be dependent on upstream signaling. Nevertheless, FOXO3a serves as an interesting potential target in therapies as it is regulated during treatment with very common anti-cancer drugs such as paclitaxel, cisplatin, docetaxel, and doxorubicin. This review aims to update the reported role of FOXO3a in prostate cancer (PCa), with a focus on its regulators that might serve as potential therapeutic agents in PCa therapy.

For years, the renin-angiotensin system (RAS) has been perceived as a system whose role is to primarily modulate the functioning of the cardiovascular system. Years of research into the role of RAS have provided the necessary data to confirm that the role of RAS is very complex and not limited to the cardiovascular system. The presence of individual elements of the renin-angiotensin (RA) system allows to control many processes, ranging from the memorization to pro-cancer processes. Maintaining the proportions between the individual axes of the RA system allows for achieving a balance, often called homeostasis. Thus, any disturbance in the expression or activity of individual RAS elements leads to pathophysiological processes.

Deoxynivalenol (DON), known as vomitoxin, a type B trichothecene, is produced by Fusarium. DON frequently contaminates cereal grains such as wheat, maize, oats, barley, rye, and rice. At the molecular level, it induces ribosomal stress, inflammation and apoptosis in eukaryotic cells. Our findings indicate that DON modulates the viability of prostate cancer (PCa) cells and that the response to a single high dose of DON is dependent on the androgen-sensitivity of cells. DON appears to increase reactive oxygen species (ROS) production in cells, induces DNA damage, and triggers apoptosis. The effects of DON application in PCa cells are influenced by the mitogen-activated protein kinase (MAPK) and NFΚB- HIF-1α signaling pathways. Our results indicate that p53 is a crucial factor in DON-associated apoptosis in PCa cells. Taken together, our findings show that a single exposure to high concentrations of DON (2–5 µM) modulates the progression of PCa.