Fig. 4: (S)-CRZ inhibits ferroptosis by decreasing PE-O-PUFA.
From: Crizotinib and its enantiomer suppress ferroptosis by decreasing PE-O-PUFA content
A (S)-CRZ (3 μM) and (R)-CRZ (3 μM) do not affect the expression of ferroptosis-related lipid-metabolism genes validated by Western blot. (B–D) (S)-CRZ inhibits ferroptosis by decreasing PE-O-PUFA. This test consisted of unpaired independent samples of DMSO and (S)-CRZ (3 µM) groups (n = 4), and the hypothesis test used was a non-parametric test Mann-Whitney U test. Heatmap analysis showed decrease of ether-linked-PE components in lipidomic profile of HT-1080 cells upon (S)-CRZ treatment compared to DMSO group (B). Volcano plot showed differential PE components in lipidomic profile of HT-1080 cells line upon (S)-CRZ treatment compared to DMSO group (C). Amount of indicated PE-O-PUFA in HT-1080 cells were shown upon (S)-CRZ or DMSO treatment (D). E Heatmap analysis showed increase of free polyunsaturated fatty acid and LPE components in lipidomic profile of HT-1080 cells upon (S)-CRZ treatment compared to DMSO group. F Validation of Flag-AGPAT3 expression in 786-O and HT-1080 cells by Western blot. G AGPAT3 overexpression reduced potency of (S)-CRZ and (R)-CRZ towards RSL3 induced ferroptosis. H Knockout of AGPAT3 increased potency of (S)-CRZ and (R)-CRZ towards RSL3-induced ferroptosis. Cell viabilities were detected at appropriate time. Data in G, H are presented as the mean ± S.D., n = 3 independent repeats.
