Fig. 1
From: Ferroptosis in cancer therapy: a novel approach to reversing drug resistance
Mechanisms governing ferroptosis and reversing chemotherapy resistance. Three pathways initiate the process of ferroptosis and chemotherapy resistance reversal: the canonical GPX4-regulated pathway, iron metabolism pathway and lipid metabolism pathway. Regulation of the canonical GPX4-regulated pathway is as follows: ①Directly inhibit GPX4 by upregulating miR-324-3p or downregulating AR and KIF20A. ② Inhibit GSH biosynthesis by ent-kaurane diterpenoids. ③ Inhibit cystine uptake by erastin and sorafenib or upregulating miR-375 and ATF3. Regulation of the iron metabolism pathway is as follows: ④ Increase cellular LIP by DHA, downregulating DMT1 and LCN2. Regulation of the lipid metabolism pathway is as follows: ⑤ Target ACSL4 by downregulating ARF6. ⑥ Target LOX by downregulating miR-522. xCT: cystine/glutamate antiporter; ATF3: activating transcription factor 3; GSH: glutathione; GPX4: glutathione peroxidase 4; AR: androgen receptor; LIP: labile iron pool; DHA: dihydroartemisinin; DMT1: divalent metal transporter 1; LCN2: lipocalin 2; ROS: reactive oxygen species; PLOH: phospholipid alcohols; PLOOH: phospholipid hydroperoxides; PUFA: polyunsaturated fatty acid; ARF6: ADP ribosylation factor 6; ACSL4: acyl-CoA synthetase long chain family member 4; CoA: coenzyme A; LPCAT: lysophosphatidylcholine acyltransferase; PL: phospholipid; LOX: lipoxygenases; POR: cytochrome P450 oxidoreductase