Abstract
Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the most deregulated signaling pathway in prostate cancer. It controls basic processes in cells: cell proliferation and death. Any disturbances in the balance between cell death and survival might result in carcinogenesis. Deoxynivalenol (DON) is one of the most common mycotoxins, a toxic metabolites of fungi, present in our everyday diet and feed. Although previous studies reported DON to induce oxidative stress, modulate steroidogenesis, DNA damage and cell cycle modulation triggering together its toxicity, its effect on normal prostate epithelial cells is not known. The aim of the study was to evaluate the effect of DON on the apoptosis and autophagy in normal prostate epithelial cells via modulation of PI3K/Akt signaling pathway. The results showed that DON in a dose of 30 µM and 10 µM induces oxidative stress, DNA damage and cell cycle arrest in G2/M cell cycle phase. The higher concentration of DON induces apoptosis, whereas lower one autophagy in PNT1A cells, indicating that modulation of PI3K/Akt by DON results in the induction of autophagy triggering apoptosis in normal prostate epithelial cells.
Highlights
Contamination of mycotoxins in feed and food constitutes a global health care problem and environmental issue since years (Awuchi et al 2021)
Cells were cultured in RPMI 1640 medium supplemented with 10% heat-inactivated Fetal Bovine Serum (FBS), 1 mM Sodium Pyruvate, 10 mM HEPES Buffer and antibiotics
The viability of cells was once again evaluated with the chosen doses of DON and LY294002 to check how Phosphoinositide 3-kinase (PI3K) inhibitor affects viability of prostate epithelial cells (Fig. 1b)
Summary
Contamination of mycotoxins in feed and food constitutes a global health care problem and environmental issue since years (Awuchi et al 2021). Deoxynivalenol (DON), known as vomitoxin is a toxic metabolite of fungi produced mainly by F. graminearum. It contaminates cereal products and possesses the highest contamination level in feed and feedstuff products (Fisher et al 2020). Archives of Toxicology the basic processes in cells: proliferation and apoptosis. Its activation is associated with increased proliferation and decreased apoptosis of cells (Sreenivasulu et al 2021). Any modulators of PI3K/ Akt signaling pathway in normal prostate epithelial cells might participate in the process of carcinogenesis of prostate tissue. Previous studies showed that DON might induce apoptosis and autophagy in cells by modulation of PI3K/ Akt/ mechanistic target of rapamycin (mTOR) signalling pathway in porcine jejunum epithelial cell line (Zhao et al 2020). The phosphorylation of Akt was observed after DON treatment in mouse skin cells (Mishra et al 2014)
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