Fig. 3.

RSL3, TRi-1, and TRi-2 have differential cellular cytotoxicity profiles. A) Cytotoxic effects of RSL3 (pink curves, left panels), but not TRi-1 (pink curves, middle panels) or TRi-2 (pink curves, right panels), are suppressed by Fer-1 (green curves) but not by MitoTEMPO (black curves) in either A549 (top panels) or H1975 cells (bottom panels) in media not supplemented with selenium as determined 24 h after addition of compounds; four-parameter dose-response curve fit to n = 4 technical replicates; B) A549 cells (left panels), H1975 cells (middle panels) and HT1080 cells (right panels) grown with (black bars) or without (grey bars) 100 nM selenium supplementation in the growth medium were treated for 24 h as indicated whereupon viability was determined, here shown as percent of DMSO-treated controls. The additional treatments are a known inhibitor of ferroptosis (Ferrostatin-1), a strong antioxidant (NDGA), iron chelators (DFO and DPD50), an inhibitor of necrosis (Necrostatin-1), or a caspase inhibitor/apoptosis blocker (z-VAD-fmk). Data from n = 4 technical replicates are shown. Unpaired, two-tailed t-test; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 in comparison to DMSO control of same Se condition; non-significant differences are not noted. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)