The cytotoxic effects of DHA are attenuated following suppression of the UPR. (A and E) Specific siRNAs were synthesized to target ATF4, XBP1 and ATF6 in PLC cells. A total of 24 h post siRNA transfection, HepG2 and PLC/PRF/5 cells were treated with 40 or 25 µM DHA, respectively, for 24 h. (B and F) Cell viability was determined using a Cell Counting Kit-8, and (C and G) intracellular total ROS and (D and H) lipid ROS levels were determined by flow cytometry. Data are presented as the mean ± standard deviation of three repeats. ***P<0.001 vs. DHA + siNC. DHA, dihydroartemisinin; UPR, unfolded protein response; siRNA, small interfering RNA; ATF, activating transcription factor; XBP1, X box-binding protein 1; sXBP1, spliced form of XBP1; unXBP1, unspliced form of XBP1; PLC, primary liver cancer; ROS, reactive oxygen species; NC, negative control; M, % of control.