Fig. 3.
Lipoxygenases are involved in ferroptosis by system xc− inhibition. (A) Dioxygenation reaction induced by lipoxygenases. (B) G-401 cell line expressed all isoforms of ALOXs as assessed by qPCR experiment. ACTB, Beta-actin. (C) A pool of siALOX targeting all ALOX genes successfully decreased mRNA levels of ALOX genes. (D) Silencing ALOXs expression conferred resistance to IKE-induced ferroptosis, whereas it did not affect RSL3 lethality in G-401 cells. (E) Silencing ALOX15B and ALOXE3 in HT-1080 cells made cells resistant to erastin. (F) Lipoxygenase inhibitors rescued cells from erastin-induced ferroptosis. A cyclooxygenase inhibitor did not affect erastin’s lethality. (G) GFP-ALOX5 translocated to the nuclear membrane only in sensitive cells upon 10 µM erastin treatment. Bar graph: mean + SD; n = 3–4; ***P < 0.001. (H) Time course of GFP-ALOX5 translocation in HT-1080 cells upon treatment with erastin or ionomycin.