Regulatory toxicology and pharmacology : RTP

Inhibition of autophagy aggravated 4-nitrophenol-induced oxidative stress and apoptosis in NHPrE1 human normal prostate epithelial progenitor cells.

PMID 28476554


4-Nitrophenol (PNP), a well-established human carcinogen, has been proven to have detrimental effects on reproductive system of male rats in previous studies. The molecular mechanisms involved PNP-induced damage remain to be established. Autophagy can exert protective effects on various cytotoxic factors that induce injury. In the present study, we aim to investigate whether autophagy is induced by PNP and the function of autophagy in PNP-induced injury in NHPrE1, a normal human prostate epithelial progenitor cell line. Our results indicate that PNP induced oxidative stress as evidenced by increased MDA levels and decreased activity of SOD and GSH-Px. PNP also increased apoptosis of NHPrE1 cells as evidenced by western blot and Hoechst 33258 staining and activated autophagy in NHPrE1 cells detected by RT-PCR and western blot. Inhibition of autophagy by 3-MA further increased PNP-induced oxidative stress and apoptosis of NHPrE1 cells. We also found that PNP-induced apoptosis was suppressed by N-acetylcysteine, suggesting oxidative stress may play an important role in PNP cytotoxicity. Furthermore, phosphorylation of mTOR protein was inhibited by PNP, indicating that PNP might induce autophagy in NHPrE1 cells via inhibiting mTOR pathway. In conclusion, these results suggest that activation of autophagy should play a protective role in PNP-induced oxidative stress and apoptosis of NHPrE1 cells, which might be mediated through mTOR pathway.