FOXO3a/PI3K/Akt pathway participates in the ROS- induced apoptosis triggered by α-ZEL and β-ZEL.

Zearalenone (ZEN), an estrogenic mycotoxin, is one of the most common food and feed contaminants. Also, its metabolites α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL) are considered to induce oxidative stress, however its effect in prostate cells is not known yet. Our previous observations showed that forehead box transcription factor 3a (FOXO3a) expression is modified in hormone- sensitive cells in the response to mycotoxins, similar to the phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway. Thus, this study evaluated the direct molecular effect of α-ZEL and β-ZEL in a dose of 30 µM in hormone-dependent human prostate cancer (PCa) cells with the focus of the involvement of FOXO3a and PI3K/Akt signaling pathway in that effect. We observed that both active metabolites of ZEN reduced cell viability, induced oxidative stress, cell cycle arrest and apoptosis in PCa cells. Furthermore, we observed that FOXO3a as well as PI3K/Akt signaling pathway participate in ZELs induced toxicity in PCa cells, indicating that this signaling pathway might be a regulator of mycotoxin-induced toxicity generally.