Medical University of Lodz, Department of Cell Cultures and Genomic Analysis, Zeligowskiego 7/9, 90-752, Lodz, Poland.
Medical University of Lodz, Department of Comparative Endocrinology, Zeligowskiego 7/9, 90-752, Lodz, Poland.
Arch Toxicol. 2022 Jan;96(1):231-241. doi: 10.1007/s00204-021-03176-z. Epub 2021 Oct 22.
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.
磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）信号通路是前列腺癌中最失调的信号通路之一。它控制着细胞的基本过程：细胞增殖和死亡。细胞死亡和存活之间的任何平衡失调都可能导致癌变。脱氧雪腐镰刀菌烯醇（DON）是最常见的霉菌毒素之一，是真菌的有毒代谢物，存在于我们的日常饮食和饲料中。尽管先前的研究报告称 DON 会诱导氧化应激、调节类固醇生成、DNA 损伤和细胞周期调节，从而引发其毒性，但它对正常前列腺上皮细胞的影响尚不清楚。本研究旨在通过调节 PI3K/Akt 信号通路来评估 DON 对正常前列腺上皮细胞凋亡和自噬的影响。结果表明，DON 在 30µM 和 10µM 的剂量下诱导氧化应激、DNA 损伤和 G2/M 细胞周期相的细胞周期阻滞。较高浓度的 DON 诱导细胞凋亡，而较低浓度的 DON 诱导 PNT1A 细胞自噬，表明 DON 对 PI3K/Akt 的调节导致自噬触发正常前列腺上皮细胞凋亡。
