Mechanism of ferroptosis and its relationship with tumors

doi:10.3760/cma.j.issn.1673-422X.2018.10.009

Abstract

Abstract: Ferroptosis is a new type of cell death discovered in recent years. This form of irondependent cell death is morphologically and biochemically distinct from other cell death modalities, including apoptosis and necrosis. This process is accompanied by the depletion of glutathione, a decrease in glutathione peroxidase activity and the accumulation of lipid peroxidation products. Studies have found that ferroptosis can be involved in the occurrence and progression of tumor by activating different regulatory sites in the signaling pathways, which can promote tumor cell death. Therefore, to clarify ferroptosis pathway and its related mechanisms regulating tumor development may provide new ideas for clinical treatment of tumors.

Key words: Neoplasms, Ferroptosis, Glutathione peroxidase, Lipid peroxidation

Cheng Lin, Zhao Mingfeng. Mechanism of ferroptosis and its relationship with tumors[J]. Journal of International Oncology, 2018, 45(10): 619-623.

References

［1］ Galluzzi L, BravoSan Pedro JM, Vitale I, et al. Essential versus accessory aspects of cell death: recommendations of the NCCD 2015［J］. Cell Death Differ, 2015, 22(1): 58-73. DOI: 10.1038/cdd.2014.137. ［2］ Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an irondependent form of nonapoptotic cell death［J］. Cell, 2012, 149(5): 1060-1072. DOI: 10.1016/j.cell.2012.03.042. ［3］ Dolma S, Lessnick SL, Hahn WC, et al. Identification of genotypeselective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells［J］. Cancer Cell, 2003, 3(3): 285-296. ［4］ Yang WS, Stockwell BR. Synthetic lethal screening identifies compounds activating irondependent, nonapoptotic cell death in oncogenicRASharboring cancer cells［J］. Chem Biol, 2008, 15(3): 234-245. DOI: 10.1016/j.chembiol.2008.02.010. ［5］ Yang WS, Stockwell BR. Ferroptosis: death by lipid peroxidation［J］. Trends Cell Biol, 2016, 26(3): 165-176. DOI: 10.1016/j.tcb.2015.10.014. ［6］ Dixon SJ, Stockwell BR. The role of iron and reactive oxygen species in cell death［J］. Nat Chem Biol, 2014, 10(1): 9-17. DOI: 10.1038/nchembio.1416. ［7］ Hou W, Xie Y, Song X, et al. Autophagy promotes ferroptosis by degradation of ferritin［J］. Autophagy, 2016, 12(8): 1425-1428. DOI: 10.1080/15548627.2016.1187366. ［8］ Ryu MS, Zhang D, Protchenko O, et al. PCBP1 and NCOA4 regulate erythroid iron storage and heme biosynthesis［J］. J Clin Invest, 2017, 127(5): 1786-1797. DOI: 10.1172/JCI90519. ［9］ Dixon SJ, Patel DN, Welsch M, et al. Pharmacological inhibition of cystineglutamate exchange induces endoplasmic reticulum stress and ferroptosis［J］. Elife, 2014, 3: e02523. DOI: 10.7554/eLife.02523. ［10］ Cramer SL, Saha A, Liu J, et al. Systemic depletion of Lcyst(e)ine with cyst(e)inase increases reactive oxygen species and suppresses tumor growth［J］. Nat Med, 2017, 23(1): 120-127. DOI: 10.1038/nm.4232. ［11］ Louandre C, Marcq I, Bouhlal H, et al. The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells［J］. Cancer Lett, 2015, 356(2 Pt B): 971-977. DOI: 10.1016/j.canlet.2014.11.014. ［12］ Cozza G, Rossetto M, BoselloTravain V, et al. Glutathione peroxidase 4catalyzed reduction of lipid hydroperoxides in membranes: the polar head of membrane phospholipids binds the enzyme and addresses the fatty acid hydroperoxide group toward the redox center［J］. Free Radic Biol Med, 2017, 112: 1-11. DOI: 10.1016/j.freeradbiomed.2017.07.010. ［13］ Shintoku R, Takigawa Y, Yamada K, et al. Lipoxygenasemediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3［J］. Cancer Sci, 2017, 108(11): 2187-2194. DOI: 10.1111/cas.13380. ［14］ Woo JH, Shimoni Y, Yang WS, et al. Elucidating compound mechanism of action by network perturbation analysis［J］. Cell, 2015, 162(2): 441-451. DOI: 10.1016/j.cell.2015.05.056. ［15］ Kagan VE, Mao G, Qu F, et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis［J］. Nat Chem Biol, 2017, 13(1): 81-90. DOI: 10.1038/nchembio.2238. ［16］ Doll S, Proneth B, Tyurina YY, et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition［J］. Nat Chem Biol, 2017, 13(1): 91-98. DOI: 10.1038/nchembio.2239. ［17］ Dixon SJ, Winter GE, Musavi LS, et al. Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death［J］. Acs Chem Biol, 2015, 10(7): 16041609. DOI: 10.1021/acschembio.5b00245. ［18］ Wenzel SE, Tyurina YY, Zhao J, et al. PEBP1 wardens ferroptosis by enabling lipoxygenase generation of lipid death signals［J］. Cell, 2017, 171(3): 628-641. e626. DOI: 10.1016/j.cell.2017.09.044. ［19］ Jiang L, Kon N, Li T, et al. Ferroptosis as a p53mediated activity during tumour suppression［J］. Nature, 2015, 520(7545): 57-62. DOI: 10.1038/nature14344. ［20］ Gao M, Monian P, Quadri N, et al. Glutaminolysis and transferrin regulate ferroptosis［J］. Mol Cell, 2015, 59(2): 298-308. DOI: 10.1016/j.molcel.2015.06.011. ［21］ Ou Y, Wang SJ, Li D, et al. Activation of SAT1 engages polyamine metabolism with p53mediated ferroptotic responses［J］. Proc Natl Acad Sci U S A, 2016, 113(44): E6806-E6812. DOI: 10.1073/pnas.1607152113. ［22］ Basuli D, Tesfay L, Deng Z, et al. Iron addiction: a novel therapeutic target in ovarian cancer［J］. Oncogene, 2017, 36(29): 4089-4099. DOI: 10.1038/onc.2017.11. ［23］ Housman G, Byler S, Heerboth S, et al. Drug resistance in cancer: an overview［J］. Cancers (Basel), 2014, 6(3): 1769-1792. DOI: 10.3390/cancers6031769. ［24］ Chekhun VF, Lozovska YV, Burlaka AP, et al. Peculiarities of antioxidant system and iron metabolism in organism during development of tumor resistance to cisplatin［J］. Exp Oncol, 2014, 36(3): 196-201. ［25］ Li J, He K, Liu P, et al. Iron participated in breast cancer chemoresistance by reinforcing IL6 paracrine loop［J］. Biochem Biophys Res Commun, 2016, 475(2): 154-160. DOI: 10.1016/j.bbrc.2016.05.064. ［26］ Viswanathan VS, Ryan MJ, Dhruv HD, et al. Dependency of a therapyresistant state of cancer cells on a lipid peroxidase pathway［J］. Nature, 2017, 547(7664): 453-457. DOI: 10.1038/nature23007. ［27］ Sato M, Kusumi R, Hamashima S, et al. The ferroptosis inducer erastin irreversibly inhibits system Xc and synergizes with cisplatin to increase cisplatin′s cytotoxicity in cancer cells［J］. Sci Rep, 2018, 8(1): 968. DOI: 10.1038/s41598018192134. ［28］ Sato H, Shiiya A, Kimata M, et al. Redox imbalance in cystine/glutamate transporterdeficient mice［J］. J Biol Chem, 2005, 280(45): 37423-37429. DOI: 10.1074/jbc.M506439200. ［29］ Probst L, Dchert J, Schenk B, et al. Lipoxygenase inhibitors protect acute lymphoblastic leukemia cells from ferroptotic cell death［J］. Biochem Pharmacol, 2017, 140: 41-52. DOI: 10.1016/j.bcp.2017.06.112. ［30］ Schott C, Graab U, Cuvelier N, et al. Oncogenic RAS mutants confer resistance of RMS13 rhabdomyosarcoma cells to oxidative stressinduced ferroptotic cell death［J］. Front Oncol, 2015, 5: 131. DOI: 10.3389/fonc.2015.00131. ［31］ Yang WS, SriRamaratnam R, Welsch ME, et al. Regulation of ferroptotic cancer cell death by GPX4［J］. Cell, 2014, 156(1-2): 317-331. DOI: 10.1016/j.cell.2013.12.010. ［32］ Hangauer MJ, Viswanathan VS, Ryan MJ, et al. Drugtolerant persister cancer cells are vulnerable to GPX4 inhibition［J］. Nature, 2017, 551(7679): 247-250. DOI: 10.1038/nature24297.

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