Effect of aucubin on ferroptosis in glioma cells

NIU Guo-dong; SONG Zhi-yuan; REN Hong-bo; QU Da-cheng

doi:10.13798/j.issn.1009-153X.2025.02.007

Abstract：Objective To explore the effect and mechanism of aucubin(Auc)on ferroptosis in glioma cells.Methods Glioma cell line U251 cells were cultured in vitro and divided into the control group(without any intervention),the Auc group(20 μmol/L Auc added to the medium),the ferroptosis inhibitor group(20 μmol/L Auc and 1 μmol/L ferroptosis inhibitor ferrostatin-1 added to the medium),and the PERK inhibitor group(20 μmol/L Auc and 5 μmol/L PERK inhibitor GSK2606414 added to the medium).Cell viability was detected by CCK-8 assay;cell morphology was observed by transmission electron microscopy;the level of reactive oxygen species(ROS)in cells was determined by flow cytometry;the level of glutathione(GSH)in cells was measured by GSH detection kit;the expression of protein kinase R-like endoplasmic reticulum kinase(PERK)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)pathway-related proteins was detected by Western blotting.Results Compared with the control group,the viability and GSH level of U251 cells in the Auc group were significantly decreased(P<0.05),while the ROS level and the expression levels of PERK,p-Nrf2/Nrf2,and HO-1 proteins were significantly increased(P<0.05).Transmission electron microscopy observation revealed that the mitochondrial volume decreased,the membrane density increased,the cristae decreased,and the outer membrane ruptured in U251 cells after treatment of Auc.Ferrostatin-1 and GSK2606414 significantly attenuated the induction effect of Auc on ferroptosis of U251 cells(P<0.05).Conclusion Auc promotes ferroptosis of glioma cells U251 by activating the PERK/Nrf2/HO-1 signaling pathway,thereby inhibiting the viability of glioma cells.