{"title":"Redox Signaling in Doxorubicin-Induced Ferroptosis","authors":"E. Ros","doi":"10.20455/ros.2023.n803","DOIUrl":null,"url":null,"abstract":"Doxorubicin is among the most widely used anticancer drugs; however, its clinical use is associated with cardiomyopathy and heart failure. Studies show ferroptosis as a pivotal form of cell death underlying doxorubicin cardiomyopathy. Recently, multiple redox signaling pathways have been discovered to underly doxorubicin-induced ferroptosis. This Cutting-Edge Research Highlights discusses these latest advances, focusing on pathways involving Nrf2/HO-1, GPx4, and Alas1/heme synthesis.\n(First online: February 19, 2023)\nREFERENCES \n\nZhu H, Sarkar S, Scott L, Danelisen I, Trush MA, Jia Z, et al. Doxorubicin Redox biology: redox cycling, topoisomerase inhibition, and oxidative stress. React Oxyg Species (Apex) 2016; 1(3):189–98. doi: https://dx.doi.org/10.20455/ros.2016.835\nHiggins AY, O'Halloran TD, Chang JD. Chemotherapy-induced cardiomyopathy. Heart Fail Rev 2015; 20(6):721–30. doi: https://dx.doi.org/10.1007/s10741-015-9502-y\nPage RL, 2nd, O'Bryant CL, Cheng D, Dow TJ, Ky B, Stein CM, et al. Drugs that may cause or exacerbate heart failure: a scientific statement from the American Heart Association. Circulation 2016; 134(6):e32–69. doi: https://dx.doi.org/10.1161/CIR.0000000000000426\nFang X, Wang H, Han D, Xie E, Yang X, Wei J, et al. Ferroptosis as a target for protection against cardiomyopathy. Proc Natl Acad Sci USA 2019; 116(7):2672–80. doi: https://dx.doi.org/10.1073/pnas.1821022116\nDixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 2012; 149(5):1060–72. doi: https://dx.doi.org/10.1016/j.cell.2012.03.042\nYang WS, Kim KJ, Gaschler MM, Patel M, Shchepinov MS, Stockwell BR. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc Natl Acad Sci USA 2016; 113(34):E4966–75. doi: https://dx.doi.org/10.1073/pnas.1603244113\nKagan VE, Mao G, Qu F, Angeli JP, Doll S, Croix CS, et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat Chem Biol 2017; 13(1):81–90. doi: https://dx.doi.org/10.1038/nchembio.2238\nIchikawa Y, Ghanefar M, Bayeva M, Wu R, Khechaduri A, Naga Prasad SV, et al. Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation. J Clin Invest 2014; 124(2):617–30. doi: https://dx.doi.org/10.1172/JCI72931\nTadokoro T, Ikeda M, Ide T, Deguchi H, Ikeda S, Okabe K, et al. Mitochondria-dependent ferroptosis plays a pivotal role in doxorubicin cardiotoxicity. JCI Insight 2020; 5(9). doi: https://dx.doi.org/10.1172/jci.insight.132747\nAbe K, Ikeda M, Ide T, Tadokoro T, Miyamoto HD, Furusawa S, et al. Doxorubicin causes ferroptosis and cardiotoxicity by intercalating into mitochondrial DNA and disrupting Alas1-dependent heme synthesis. Sci Signal 2022; 15(758):eabn8017. doi: https://dx.doi.org/10.1126/scisignal.abn8017\n","PeriodicalId":91793,"journal":{"name":"Reactive oxygen species (Apex, N.C.)","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reactive oxygen species (Apex, N.C.)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.20455/ros.2023.n803","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Doxorubicin is among the most widely used anticancer drugs; however, its clinical use is associated with cardiomyopathy and heart failure. Studies show ferroptosis as a pivotal form of cell death underlying doxorubicin cardiomyopathy. Recently, multiple redox signaling pathways have been discovered to underly doxorubicin-induced ferroptosis. This Cutting-Edge Research Highlights discusses these latest advances, focusing on pathways involving Nrf2/HO-1, GPx4, and Alas1/heme synthesis.
(First online: February 19, 2023)
REFERENCES
Zhu H, Sarkar S, Scott L, Danelisen I, Trush MA, Jia Z, et al. Doxorubicin Redox biology: redox cycling, topoisomerase inhibition, and oxidative stress. React Oxyg Species (Apex) 2016; 1(3):189–98. doi: https://dx.doi.org/10.20455/ros.2016.835
Higgins AY, O'Halloran TD, Chang JD. Chemotherapy-induced cardiomyopathy. Heart Fail Rev 2015; 20(6):721–30. doi: https://dx.doi.org/10.1007/s10741-015-9502-y
Page RL, 2nd, O'Bryant CL, Cheng D, Dow TJ, Ky B, Stein CM, et al. Drugs that may cause or exacerbate heart failure: a scientific statement from the American Heart Association. Circulation 2016; 134(6):e32–69. doi: https://dx.doi.org/10.1161/CIR.0000000000000426
Fang X, Wang H, Han D, Xie E, Yang X, Wei J, et al. Ferroptosis as a target for protection against cardiomyopathy. Proc Natl Acad Sci USA 2019; 116(7):2672–80. doi: https://dx.doi.org/10.1073/pnas.1821022116
Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 2012; 149(5):1060–72. doi: https://dx.doi.org/10.1016/j.cell.2012.03.042
Yang WS, Kim KJ, Gaschler MM, Patel M, Shchepinov MS, Stockwell BR. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc Natl Acad Sci USA 2016; 113(34):E4966–75. doi: https://dx.doi.org/10.1073/pnas.1603244113
Kagan VE, Mao G, Qu F, Angeli JP, Doll S, Croix CS, et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat Chem Biol 2017; 13(1):81–90. doi: https://dx.doi.org/10.1038/nchembio.2238
Ichikawa Y, Ghanefar M, Bayeva M, Wu R, Khechaduri A, Naga Prasad SV, et al. Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation. J Clin Invest 2014; 124(2):617–30. doi: https://dx.doi.org/10.1172/JCI72931
Tadokoro T, Ikeda M, Ide T, Deguchi H, Ikeda S, Okabe K, et al. Mitochondria-dependent ferroptosis plays a pivotal role in doxorubicin cardiotoxicity. JCI Insight 2020; 5(9). doi: https://dx.doi.org/10.1172/jci.insight.132747
Abe K, Ikeda M, Ide T, Tadokoro T, Miyamoto HD, Furusawa S, et al. Doxorubicin causes ferroptosis and cardiotoxicity by intercalating into mitochondrial DNA and disrupting Alas1-dependent heme synthesis. Sci Signal 2022; 15(758):eabn8017. doi: https://dx.doi.org/10.1126/scisignal.abn8017