From: Harnessing ferroptosis for enhanced sarcoma treatment: mechanisms, progress and prospects
Compound | Mechanism | Effect | Cell model | Refs. |
---|---|---|---|---|
â‘ Ferroptosis inhibitors in sarcoma | ||||
Bathophenanthrolined-isulfonic acid (BPS) | Iron chelator | Fe2+ ↓ | C2C12, U57810 (rhabdomyosarcoma) | [92] |
Bisindolylmaleimide I and Gö6976 | Protein kinase C inhibitor | Lipid peroxides ↓ | RD, RH18, RH30 | [151] |
Deferoxamine (DFO) | Iron chelator | Fe2+ ↓ | MG63, HOS (Osteosarcoma); HT1080 (fibrosarcoma) | |
Diphenyleneiodonium chloride (DPI) and GKT137831 | NOX inhibitor | NOX-mediated lipid peroxidation ↓, ROS ↓ | RD, RH18, RH30 | [151] |
Fanconi anemia complementation group D2 (FANCD2) | JAK2/STAT3 pathway inhibitor, FTH1 ↑, GPX4 ↑, COX2 ↓, LIP ↓ | GPX4 ↑, Fe2+ ↓, ROS ↓ | MG-63, U2OS, hFOB1.19 (Osteosarcoma) | [172] |
Ferrostatin-1 | Radical-trapping antioxidants | ROS ↓, lipid peroxides ↓ | HT1080, MG63, HOS, C2C12, RD, RH18, RH30, HEK-29, HT22, etc (various sarcomas) | |
Liproxstatin-1 | Radical-trapping antioxidants | ROS ↓, lipid peroxides ↓ | HT1080, MG63, HOS, HEK-29, HT22 (various sarcomas) | |
LncRNA- SNHG14 | Down-regulating miR-206 | GSH ↑ | NR-SJSA1 (nutlin3a-resistant osteosarcoma) | [174] |
Mitochondrial NADP + -dependent isocitrate dehydrogenase (IDH2) | NADPH production | GSH ↑ | HT1080 (fibrosarcoma); Hepa1-6 (hepatoma) | [175] |
N-acetyl cysteine (NAC), Glutathione (GSH) | Antioxidant, GSH supplement | GSH ↑, ROS ↓ | HT1080, C2C12, U57810 (rhabdomyosarcoma) | |
Pifithrin-α | p53 inhibitor | GSH ↑ | MG63, HOS (Osteosarcoma) | [146] |
Vitamin E and tocopherols | Antioxidant, LOX inhibitor | ROS ↓, lipid peroxides ↓ | MG63, HOS (Osteosarcoma), Pfa1 | |
ZnPPIX | Down-regulating HMOX1 | Fe2+ ↓, GPX4 ↑, ROS ↓, MDA ↓ | SW872 (liposarcoma), MG63 (osteosarcoma) | [144] |
â‘¡ Ferroptosis inhibitors in other cells | ||||
1-methyl tryptophan | Indoleamine 2, 3-dioxygenase (IDO) inhibitor, up-regulating SLC7A11, reduction of nitrative stress | GSH ↑ | LO2 | [176] |
AA-861 | 5-LOX inhibitor | ROS ↓, lipid peroxides ↓ | HEK-293 T, G401 | |
Baicalein | 12/15-LOX inhibitor | ROS ↓, lipid peroxides ↓ | PANC1, BxPc3; Jurkat, Molt-4 | |
Butylated hydroxyanisole and butylated hydroxytoluene | Antioxidant | ROS ↓, lipid peroxides ↓ | HT1080; male C57BL/6 J mice | |
β-mercaptoethanol (2ME) | Reduction of cystine to cysteine | GSH ↑ | BMDMΦ and OT-1 CD8+ T cells | |
CoQ10, idebenone | Antioxidant | ROS ↓, lipid peroxides ↓ | U-2 OS, NCI-H460, NCI-H2291, NCI-H1703, NCI-H446, HT1080 | |
Dopamine | Improvement of stability of GPX4 | GPX4 ↑ | HEK293, PANC1, HEY, MEF | [183] |
Selenium | Active group of GPX4 | GPX4 ↑ | HT-1080, MEFs | [58] |
Zileuton | 5-LOX inhibitor | ROS ↓, lipid peroxides ↓ | Pfa1, HT22 |