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Research progress on ferroptosis in radiosensitivity of malignant tumors
Lin Wei, Wu Yadong
School of Stomatology, Guizhou Medical University, Department of oral and maxillofacial surgery, Affiliated Stomatological Hospital, Guizhou Medical University, Guiyang 550000, China
Abstract As one of the most effective treatments for cancer, radiotherapy(RT)can eliminate the tumor cells and improve the survival rate of cancer patients. However, radiation resistance of tumor cells remarkably reduces the efficacy of RT. Therefore, it is significant to investigate the resistance mechanism and explore corresponding therapy for cancer. Ferroptosis is a novel mode of programmed cell death. Numerous studies have indicated an intimate connection between ferroptosis and tumor radiosensitivity. The mechanism involves lipid reactive oxygen species accumulation, glutathione metabolism and iron metabolism. It has been reported that ferroptosis inducers can act effectively and synergistically with RT, promote radiosensitivity and further improve tumor prognosis. In this article, relevant mechanisms and research progress were reviewed, and the future development direction of this field was discussed, aiming to provide reference for clinical trials and mechanism research of RT for malignant tumors.
Lin Wei,Wu Yadong. Research progress on ferroptosis in radiosensitivity of malignant tumors[J]. Chinese Journal of Radiation Oncology, 2023, 32(6): 572-576.
Lin Wei,Wu Yadong. Research progress on ferroptosis in radiosensitivity of malignant tumors[J]. Chinese Journal of Radiation Oncology, 2023, 32(6): 572-576.
[1] Prajapati J, Goswami D, Rawal RM.Endophytic fungi: a treasure trove of novel anticancer compounds[J]. Curr Res Pharmacol Drug Discov, 2021,2:100050. DOI: 10.1016/j.crphar.2021.100050. [2] Chandra S.Endophytic fungi: novel sources of anticancer lead molecules[J]. Appl Microbiol Biotechnol, 2012,95(1):47-59. DOI: 10.1007/s00253-012-4128-7. [3] Gong LY, Zhang YJ, Liu CC, et al.Application of radiosensitizers in cancer radiotherapy[J]. Int J Nanomedicine, 2021,16:1083-1102. DOI: 10.2147/IJN.S290438. [4] Peters LJ, Withers HR, Thames HD, et al.Tumor radioresistance in clinical radiotherapy[J]. Int J Radiat Oncol Biol Phys, 1982,8(1):101-108. DOI: 10.1016/0360-3016(82)90392-3. [5] West CM, Davidson SE, Hendry JH, et al.Prediction of cervical carcinoma response to radiotherapy[J]. Lancet, 1991,338(8770):818. DOI: 10.1016/0140-6736(91)90700-y. [6] 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. [7] Zhang Z, Lu ML, Chen CL, et al.Holo-lactoferrin: the link between ferroptosis and radiotherapy in triple-negative breast cancer[J]. Theranostics, 2021,11(7):3167-3182. DOI: 10.7150/thno.52028. [8] Tomita K, Nagasawa T, Kuwahara Y, et al. MiR-7-5p is involved in ferroptosis signaling and radioresistance thru the generation of ROS in radioresistant HeLa and SAS cell lines[J]. Int J Mol Sci, 2021,22(15)DOI: 10.3390/ijms22158300. [9] Ye LF, Chaudhary KR, Zandkarimi F, et al.Radiation-induced lipid peroxidation triggers ferroptosis and synergizes with ferroptosis inducers[J]. ACS Chem Biol, 2020,15(2):469-484. DOI: 10.1021/acschembio.9b00939. [10] Lang XT, Green MD, Wang WM, et al.Radiotherapy and immunotherapy promote tumoral lipid oxidation and ferroptosis via synergistic repression of SLC7A11[J]. Cancer Discov, 2019,9(12):1673-1685. DOI: 10.1158/2159-8290.CD-19-0338. [11] Stockwell BR, Friedmann Angeli JP, Bayir H, et al.Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease[J]. Cell, 2017,171(2):273-285. DOI: 10.1016/j.cell.2017.09.021. [12] 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. [13] Manz DH, Blanchette NL, Paul BT, et al.Iron and cancer: recent insights[J]. Ann N Y Acad Sci, 2016,1368(1):149-161. DOI: 10.1111/nyas.13008. [14] Jiang L, Kon N, Li TY, et al.Ferroptosis as a p53-mediated activity during tumour suppression[J]. Nature, 2015,520(7545):57-62. DOI: 10.1038/nature14344. [15] Bellezza I, Giambanco I, Minelli A, et al.Nrf2-Keap1 signaling in oxidative and reductive stress[J]. Biochim Biophys Acta Mol Cell Res, 2018,1865(5):721-733. DOI: 10.1016/j.bbamcr.2018.02.010. [16] Chen Y, Liu Y, Lan T, et al.Quantitative profiling of protein carbonylations in ferroptosis by an aniline-derived probe[J]. J Am Chem Soc, 2018,140(13):4712-4720. DOI: 10.1021/jacs.8b01462. [17] Donlon NE, Power R, Hayes C, et al.Radiotherapy, immunotherapy, and the tumour microenvironment: turning an immunosuppressive milieu into a therapeutic opportunity[J]. Cancer Lett, 2021,502:84-96. DOI: 10.1016/j.canlet.2020.12.045. [18] Morgan MA, Lawrence TS.Molecular pathways: overcoming radiation resistance by targeting DNA damage response pathways[J]. Clin Cancer Res, 2015,21(13):2898-2904. DOI: 10.1158/1078-0432.CCR-13-3229. [19] Baidoo KE, Yong K, Brechbiel MW.Molecular pathways: targeted α-particle radiation therapy[J]. Clin Cancer Res, 2013,19(3):530-537. DOI: 10.1158/1078-0432.CCR-12-0298. [20] Commoner B, Townsend J, Pake Ge.Free radicals in biological materials[J]. Nature, 1954,174(4432):689-691. DOI: 10.1038/174689a0. [21] Srinivas US, Tan B, Vellayappan BA, et al.ROS and the DNA damage response in cancer[J]. Redox Biol, 2019,25:101084. DOI: 10.1016/j.redox.2018.101084. [22] Fan PC, Zhang Y, Wang Y, et al.Quantitative proteomics reveals mitochondrial respiratory chain as a dominant target for carbon ion radiation: delayed reactive oxygen species generation caused DNA damage[J]. Free Radic Biol Med, 2019,130:436-445. DOI: 10.1016/j.freeradbiomed.2018.10.449. [23] Sies H, Jones DP.Reactive oxygen species (ROS) as pleiotropic physiological signalling agents[J]. Nat Rev Mol Cell Biol, 2020,21(7):363-383. DOI: 10.1038/s41580-020-0230-3. [24] Cerda MB, Lloyd R, Batalla M, et al.Silencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatin[J]. Cancer Lett, 2017,388:312-319. DOI: 10.1016/j.canlet.2016.12.009. [25] Zhang XH, Li X, Zheng CY, et al.Ferroptosis, a new form of cell death defined after radiation exposure[J]. Int J Radiat Biol, 2022,98(7):1201-1209. DOI: 10.1080/09553002.2022.2020358. [26] Stockwell BR, Friedmann Angeli JP, Bayir H, et al.Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease[J]. Cell, 2017,171(2):273-285. DOI: 10.1016/j.cell.2017.09.021. [27] Lei G, Zhang YL, Koppula P, et al.The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression[J]. Cell Res, 2020,30(2):146-162. DOI: 10.1038/s41422-019-0263-3. [28] Sato H, Tamba M, Ishii T, et al.Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins[J]. J Biol Chem, 1999,274(17):11455-11458. DOI: 10.1074/jbc.274.17.11455. [29] Yang WS, Kim KJ, Gaschler MM, et al.Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis[J]. Proc Natl Acad Sci U S A, 2016,113(34):E4966-4975. DOI: 10.1073/pnas.1603244113. [30] 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. [31] Liu MR, Zhu WT, Pei DS. System Xc(-): a key regulatory target of ferroptosis in cancer[J]. Invest New Drugs, 2021,39(4):1123-1131. DOI: 10.1007/s10637-021-01070-0. [32] Feng L, Zhao KK, Sun LC, et al.SLC7A11 regulated by NRF2 modulates esophageal squamous cell carcinoma radiosensitivity by inhibiting ferroptosis[J]. J Transl Med, 2021,19(1):367. DOI: 10.1186/s12967-021-03042-7. [33] Imoto S, Shibuya Y, Kono M, et al.After haemin treatment intracellular non-haem iron increases prior to haem oxygenase-1 induction: a study in human monocytic cell line THP-1[J]. Transfus Apher Sci, 2019,58(6):102662. DOI: 10.1016/j.transci.2019.10.004. [34] Wan JR, Ren HL, Wang J.Iron toxicity, lipid peroxidation and ferroptosis after intracerebral haemorrhage[J]. Stroke Vasc Neurol, 2019,4(2):93-95. DOI: 10.1136/svn-2018-000205. [35] Xu Y, Wang Q, Li XZ, et al.Itraconazole attenuates the stemness of nasopharyngeal carcinoma cells via triggering ferroptosis[J]. Environ Toxicol, 2021,36(2):257-266. DOI: 10.1002/tox.23031. [36] Ma SM, Fu XX, Liu L, et al.Iron-dependent autophagic cell death induced by radiation in MDA-MB-231 breast cancer cells[J]. Front Cell Dev Biol, 2021,9:723801. DOI: 10.3389/fcell.2021.723801. [37] Almahi WA, Yu KN, Mohammed F, et al.Hemin enhances radiosensitivity of lung cancer cells through ferroptosis[J]. Exp Cell Res, 2022,410(1):112946. DOI: 10.1016/j.yexcr.2021.112946. [38] NaveenKumar SK, Hemshekhar M, Kemparaju K, et al. Hemin-induced platelet activation and ferroptosis is mediated through ROS-driven proteasomal activity and inflammasome activation: protection by melatonin[J]. Biochim Biophys Acta Mol Basis Dis, 2019,1865(9):2303-2316. DOI: 10.1016/j.bbadis.2019.05.009. [39] Muller PA, Vousden KH. p53 mutations in cancer[J]. Nat Cell Biol, 2013,15(1):2-8. DOI: 10.1038/ncb2641. [40] Lee JM, Bernstein A. p53 mutations increase resistance to ionizing radiation[J]. Proc Natl Acad Sci U S A, 1993,90(12):5742-5746. DOI: 10.1073/pnas.90.12.5742. [41] Tarangelo A, Magtanong L, Bieging-Rolett KT, et al.p53 suppresses metabolic stress-induced ferroptosis in cancer cells[J]. Cell Rep, 2018,22(3):569-575. DOI: 10.1016/j.celrep.2017.12.077. [42] Lei G, Zhang YL, Hong T, et al.Ferroptosis as a mechanism to mediate p53 function in tumor radiosensitivity[J]. Oncogene, 2021,40(20):3533-3547. DOI: 10.1038/s41388-021-01790-w. [43] Kawasaki Y, Okumura H, Uchikado Y, et al.Nrf2 is useful for predicting the effect of chemoradiation therapy on esophageal squamous cell carcinoma[J]. Ann Surg Oncol, 2014,21(7):2347-2352. DOI: 10.1245/s10434-014-3600-2. [44] Zhang B, Fan XL, Wang Z, et al.Alpinumisoflavone radiosensitizes esophageal squamous cell carcinoma through inducing apoptosis and cell cycle arrest[J]. Biomed Pharmacother, 2017,95:199-206. DOI: 10.1016/j.biopha.2017.08.048. [45] Dodson M, Castro-Portuguez R, Zhang DD.NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis[J]. Redox Biol, 2019,23:101107. DOI: 10.1016/j.redox.2019.101107. [46] Xia D, Zhang XR, Ma YL, et al.Nrf2 promotes esophageal squamous cell carcinoma (ESCC) resistance to radiotherapy through the CaMKIIα-associated activation of autophagy[J]. Cell Biosci, 2020,10:90. DOI: 10.1186/s13578-020-00456-6. [47] Lisman J, Yasuda R, Raghavachari S.Mechanisms of CaMKII action in long-term potentiation[J]. Nat Rev Neurosci, 2012,13(3):169-182. DOI: 10.1038/nrn3192. [48] Koppula P, Lei G, Zhang YL, et al.A targetable CoQ-FSP1 axis drives ferroptosis- and radiation-resistance in KEAP1 inactive lung cancers[J]. Nat Commun, 2022,13(1):2206. DOI: 10.1038/s41467-022-29905-1. [49] Zhao YC, Li YQ, Zhang RF, et al.The role of erastin in ferroptosis and its prospects in cancer therapy[J]. Onco Targets Ther, 2020,13:5429-5441. DOI: 10.2147/OTT.S254995. [50] Shibata Y, Yasui H, Higashikawa K, et al.Erastin, a ferroptosis-inducing agent, sensitized cancer cells to X-ray irradiation via glutathione starvation in vitro and in vivo[J]. PLoS One, 2019,14(12):e0225931. DOI: 10.1371/journal.pone.0225931. [51] Pan XF, Lin ZX, Jiang DX, et al.Erastin decreases radioresistance of NSCLC cells partially by inducing GPX4-mediated ferroptosis[J]. Oncol Lett, 2019,17(3):3001-3008. DOI: 10.3892/ol.2019.9888. [52] Qiu C, Zhang X, Huang B, et al.Disulfiram, a ferroptosis inducer, triggers lysosomal membrane permeabilization by up-regulating ROS in glioblastoma[J]. Onco Targets Ther, 2020,13:10631-10640. DOI: 10.2147/OTT.S272312. [53] Lei G, Mao C, Yan YL, et al.Ferroptosis, radiotherapy, and combination therapeutic strategies[J]. Protein Cell, 2021,12(11):836-857. DOI: 10.1007/s13238-021-00841-y. [54] Pavlopoulou A, Bagos PG, Koutsandrea V, et al.Molecular determinants of radiosensitivity in normal and tumor tissue: a bioinformatic approach[J]. Cancer Lett, 2017,403:37-47. DOI: 10.1016/j.canlet.2017.05.023.
2023, Vol. 32 
