Fig. 4

Inhibition of PERK-ATF4 signaling enhanced DHA-induced ferroptosis in glioma cells. A, DFO inhibited the synergistic effects on glioma cell death of DHA combined with PERKI. B, (a) PERKi enhanced DHA-induced U251 cell ROS generation. (b) time course of ROS generation in U251 cells treated with 20 μM DHA combined with 10 μM PERKi. C, DFO suppressed the synergistic effects on ROS production of DHA combined with PERKi. D, (a) PERKi enhanced DHA-induced U251 cell MDA generation. (b) Time course of MDA generation in U251 cells treated with 20 μM DHA combined with 10 μM PERKi. E, ATF4 siRNA enhanced DHA-induced ROS (a), MDA (b) and lipid ROS (c) generation in glioma cells as well as cell death (d). *, P < 0.05; **, P < 0.01; ***, P < 0.001, compared to control. Data were mean ± SD from three independent experiments. n = 3 for all bar graphs