The double faced role of xanthine oxidoreductase in cancer.
ROS
cancer therapy
uric acid
xanthine oxidoreductase (XOR)
Journal
Acta pharmacologica Sinica
ISSN: 1745-7254
Titre abrégé: Acta Pharmacol Sin
Pays: United States
ID NLM: 100956087
Informations de publication
Date de publication:
Jul 2022
Jul 2022
Historique:
received:
20
08
2021
accepted:
19
10
2021
pubmed:
24
11
2021
medline:
7
7
2022
entrez:
23
11
2021
Statut:
ppublish
Résumé
Xanthine oxidoreductase (XOR) is a critical, rate-limiting enzyme that controls the last two steps of purine catabolism by converting hypoxanthine to xanthine and xanthine to uric acid. It also produces reactive oxygen species (ROS) during the catalytic process. The enzyme is generally recognized as a drug target for the therapy of gout and hyperuricemia. The catalytic products uric acid and ROS act as antioxidants or oxidants, respectively, and are involved in pro/anti-inflammatory actions, which are associated with various disease manifestations, including metabolic syndrome, ischemia reperfusion injury, cardiovascular disorders, and cancer. Recently, extensive efforts have been devoted to understanding the paradoxical roles of XOR in tumor promotion. Here, we summarize the expression of XOR in different types of cancer and decipher the dual roles of XOR in cancer by its enzymatic or nonenzymatic activity to provide an updated understanding of the mechanistic function of XOR in cancer. We also discuss the potential to modulate XOR in cancer therapy.
Identifiants
pubmed: 34811515
doi: 10.1038/s41401-021-00800-7
pii: 10.1038/s41401-021-00800-7
pmc: PMC9253144
doi:
Substances chimiques
Reactive Oxygen Species
0
Uric Acid
268B43MJ25
Xanthine Dehydrogenase
EC 1.17.1.4
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1623-1632Informations de copyright
© 2021. The Author(s), under exclusive licence to CPS and SIMM.
Références
Bortolotti M, Polito L, Battelli MG, Bolognesi A. Xanthine oxidoreductase: one enzyme for multiple physiological tasks. Redox Biol. 2021;41:101882.
pubmed: 33578127
pmcid: 7879036
doi: 10.1016/j.redox.2021.101882
Schmidt HM, Kelley EE, Straub AC. The impact of xanthine oxidase (XO) on hemolytic diseases. Redox Biol. 2019;21:101072.
pubmed: 30580157
doi: 10.1016/j.redox.2018.101072
Harrison R. Structure and function of xanthine oxidoreductase: where are we now? Free Radic Biol Med. 2002;33:774–97.
pubmed: 12208366
doi: 10.1016/S0891-5849(02)00956-5
Giulia BM, Andrea B, Letizia P. Pathophysiology of circulating xanthine oxidoreductase: New emerging roles for a multi-tasking enzyme. Biochim Biophys Acta. 2014;1842:1502–17.
doi: 10.1016/j.bbadis.2014.05.022
Nishino T, Okamoto K, Eger BT, Pai EF, Nishino T. Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase. FEBS J. 2008;275:3278–89.
pubmed: 18513323
doi: 10.1111/j.1742-4658.2008.06489.x
Kelley EE. A new paradigm for XOR-catalyzed reactive species generation in the endothelium. Pharmacol Rep. 2015;67:669–74.
pubmed: 26321266
pmcid: 4555844
doi: 10.1016/j.pharep.2015.05.004
McManaman JL, Palmer CA, Wright RM, Neville MC. Functional regulation of xanthine oxidoreductase expression and localization in the mouse mammary gland: evidence of a role in lipid secretion. J Physiol. 2002;545:567–79.
pubmed: 12456835
pmcid: 2290700
doi: 10.1113/jphysiol.2002.027185
Ojha R, Singh J, Ojha A, Singh H, Sharma S, Nepali K. An updated patent review: xanthine oxidase inhibitors for the treatment of hyperuricemia and gout (2011-5). Expert Opin Ther Pat. 2017;27:311–45.
pubmed: 27841045
doi: 10.1080/13543776.2017.1261111
Battelli MG, Polito L, Bortolotti M, Bolognesi A. Xanthine oxidoreductase in drug metabolism: beyond a role as a detoxifying enzyme. Curr Med Chem. 2016;23:4027–36.
pubmed: 27458036
pmcid: 5345321
doi: 10.2174/0929867323666160725091915
Roberts LE, Fini MA, Derkash N, Wright RM. PD98059 enhanced insulin, cytokine, and growth factor activation of xanthine oxidoreductase in epithelial cells involves STAT3 and the glucocorticoid receptor. J Cell Biochem. 2007;101:1567–87.
pubmed: 17370312
doi: 10.1002/jcb.21272
Berry CE, Hare JM. Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. J Physiol. 2004;555:589–606.
pubmed: 14694147
doi: 10.1113/jphysiol.2003.055913
Kelley EE, Hock T, Khoo NK, Richardson GR, Johnson KK, Powell PC, et al. Moderate hypoxia induces xanthine oxidoreductase activity in arterial endothelial cells. Free Radic Biol Med. 2006;40:952–9.
pubmed: 16540390
doi: 10.1016/j.freeradbiomed.2005.11.008
Terada LS, Piermattei D, Shibao GN, McManaman JL, Wright RM. Hypoxia regulates xanthine dehydrogenase activity at pre- and posttranslational levels. Arch Biochem. Biophysics. 1997;348:163–8.
Seymour KJ, Roberts LE, Fini MA, Parmley LA, Oustitch TL, Wright RM. Stress activation of mammary epithelial cell xanthine oxidoreductase is mediated by p38 MAPK and CCAAT/enhancer-binding protein-beta. J Biol Chem. 2006;281:8545–58.
pubmed: 16452486
doi: 10.1074/jbc.M507349200
Pacher P, Nivorozhkin A, Szabo C. Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev. 2006;58:87–114.
pubmed: 16507884
doi: 10.1124/pr.58.1.6
Abrigo J, Elorza AA, Riedel CA, Vilos C, Simon F, Cabrera D, et al. Role of oxidative stress as key regulator of muscle wasting during cachexia. Oxid Med Cell Longev. 2018;2018:2063179.
pubmed: 29785242
pmcid: 5896211
doi: 10.1155/2018/2063179
Assi M, Rebillard A. The Janus-faced role of antioxidants in cancer cachexia: new insights on the established concepts. Oxid Med Cell Longev. 2016;2016:9579868.
pubmed: 27642498
pmcid: 5013212
doi: 10.1155/2016/9579868
Springer J, Tschirner A, Hartman K, Palus S, Wirth EK, Ruis SB, et al. Inhibition of xanthine oxidase reduces wasting and improves outcome in a rat model of cancer cachexia. Int J Cancer. 2012;131:2187–96.
pubmed: 22336965
doi: 10.1002/ijc.27494
Battelli MG, Bortolotti M, Polito L, Bolognesi A. Metabolic syndrome and cancer risk: the role of xanthine oxidoreductase. Redox Biol. 2019;21:101070.
pubmed: 30576922
doi: 10.1016/j.redox.2018.101070
Battelli MG, Bortolotti M, Polito L, Bolognesi A. The role of xanthine oxidoreductase and uric acid in metabolic syndrome. Biochim Biophys Acta Mol Basis Dis. 2018;1864:2557–65.
pubmed: 29733945
doi: 10.1016/j.bbadis.2018.05.003
Agarwal A, Banerjee A, Banerjee UC. Xanthine oxidoreductase: a journey from purine metabolism to cardiovascular excitation-contraction coupling. Crit Rev Biotechnol. 2011;31:264–80.
pubmed: 21774633
doi: 10.3109/07388551.2010.527823
Battelli MG, Polito L, Bortolotti M, Bolognesi A. Xanthine oxidoreductase in cancer: more than a differentiation marker. Cancer Med. 2016;5:546–57.
pubmed: 26687331
doi: 10.1002/cam4.601
Battelli MG, Polito L, Bortolotti M, Bolognesi A. Xanthine oxidoreductase-derived reactive species: physiological and pathological effects. Oxid Med Cell Longev. 2016;2016:3527579.
pubmed: 26823950
doi: 10.1155/2016/3527579
Fini MA, Elias A, Johnson RJ, Wright RM. Contribution of uric acid to cancer risk, recurrence, and mortality. Clin and Transl Med. 2012;1:16.
doi: 10.1186/2001-1326-1-16
Garcia-Gil M, Camici M, Allegrini S, Pesi R, Petrotto E, Tozzi MG. Emerging role of purine metabolizing enzymes in brain function and tumors. Int J Mol Sci. 2018;19:3598.
pmcid: 6274932
doi: 10.3390/ijms19113598
You L, Fan Y, Liu X, Shao S, Guo L, Noreldeen HAA, et al. Liquid chromatography-mass spectrometry-based tissue metabolic profiling reveals major metabolic pathway alterations and potential biomarkers of lung cancer. J Proteome Res. 2020;19:3750–60.
pubmed: 32693607
doi: 10.1021/acs.jproteome.0c00285
Linder N, Haglund C, Lundin M, Nordling S, Ristimaki A, Kokkola A, et al. Decreased xanthine oxidoreductase is a predictor of poor prognosis in early-stage gastric cancer. J Clin Pathol. 2006;59:965–71.
pubmed: 16935971
pmcid: 1860491
doi: 10.1136/jcp.2005.032524
Linder N, Martelin E, Lundin M, Louhimo J, Nordling S, Haglund C, et al. Xanthine oxidoreductase - clinical significance in colorectal cancer and in vitro expression of the protein in human colon cancer cells. Eur J Cancer. 2009;45:648–55.
pubmed: 19112016
doi: 10.1016/j.ejca.2008.10.036
Nina Linder JL, Jorma I, Mikael L, Kari O. Raivio, Heikki J. Down-regulated xanthine oxidoreductase is a feature of aggressive breast cancer. Clin Cancer Res. 2005;11:4372–81.
pubmed: 15958620
doi: 10.1158/1078-0432.CCR-04-2280
Konno H, Minamiya Y, Saito H, Imai K, Kawaharada Y, Motoyama S, et al. Acquired xanthine dehydrogenase expression shortens survival in patients with resected adenocarcinoma of lung. Tumour Biol. 2012;33:1727–32.
pubmed: 22678977
doi: 10.1007/s13277-012-0431-2
Stirpe F, Ravaioli M, Battelli MG, Musiani S, Grazi GL. Xanthine oxidoreductase activity in human liver disease. Am J Gastroenterol. 2002;97:2079–85.
pubmed: 12190180
doi: 10.1111/j.1572-0241.2002.05925.x
Sun Q, Zhang Z, Lu Y, Liu Q, Xu X, Xu J, et al. Loss of xanthine oxidoreductase potentiates propagation of hepatocellular carcinoma stem cells. Hepatology. 2020;71:2033–49.
pubmed: 31578733
doi: 10.1002/hep.30978
Chen GL, Ye T, Chen HL, Zhao ZY, Tang WQ, Wang LS, et al. Xanthine dehydrogenase downregulation promotes TGFbeta signaling and cancer stem cell-related gene expression in hepatocellular carcinoma. Oncogenesis. 2017;6:e382.
pubmed: 28945217
pmcid: 5623907
doi: 10.1038/oncsis.2017.81
Cook W, Chu R, Saksela M, Raivio K, Yeldandi A. Differential immunohistochemical localization of xanthine oxidase in normal and neoplastic human breast epithelium. Int J Oncol. 1997;11:1013–7.
pubmed: 21528298
Fini MA, Monks J, Farabaugh SM, Wright RM. Contribution of xanthine oxidoreductase to mammary epithelial and breast cancer cell differentiation in part modulates inhibitor of differentiation-1. Mol Cancer Res. 2011;9:1242–54.
pubmed: 21775420
pmcid: 3175308
doi: 10.1158/1541-7786.MCR-11-0176
Shan L, He M, Yu M, Qiu C, Lee NH, Liu ET, et al. cDNA microarray profiling of rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 7,12-dimethylbenz[a]anthracene. Carcinogenesis. 2002;23:1561–8.
pubmed: 12376462
doi: 10.1093/carcin/23.10.1561
Miao Y, Li Q, Wang J, Quan W, Li C, Yang Y, et al. Prognostic implications of metabolism-associated gene signatures in colorectal cancer. PeerJ. 2020;8:e9847.
pubmed: 32953273
pmcid: 7474523
doi: 10.7717/peerj.9847
Veljkovic A, Hadzi-Dokic J, Sokolovic D, Basic D, Velickovic-Jankovic L, Stojanovic M, et al. Xanthine oxidase/dehydrogenase activity as a source of oxidative stress in prostate cancer tissue. Diagnostics (Basel). 2020;10:668.
doi: 10.3390/diagnostics10090668
Durak İ, Işik CÜ, Canbolat O, Akyol Ö, Kavutçu M. Adenosine deaminase, 5′ nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in cancerous and noncancerous human laryngeal tissues. Free Radic Biol Med. 1993;15:681–4.
pubmed: 8138195
doi: 10.1016/0891-5849(93)90174-S
Metwally NS, Ali SA, Mohamed AM, Khaled HM, Ahmed SA. Levels of certain tumor markers as differential factors between bilharzial and non-biharzial bladder cancer among Egyptian patients. Cancer Cell Int. 2011;11:8.
pubmed: 21473769
pmcid: 3097143
doi: 10.1186/1475-2867-11-8
Kaynar H, Meral M, Turhan H, Keles M, Celik G, Akcay F. Glutathione peroxidase, glutathione-S-transferase, catalase, xanthine oxidase, Cu-Zn superoxide dismutase activities, total glutathione, nitric oxide, and malondialdehyde levels in erythrocytes of patients with small cell and non-small cell lung cancer. Cancer Lett. 2005;227:133–9.
pubmed: 16112416
doi: 10.1016/j.canlet.2004.12.005
Tsao SM, Yin MC, Liu WH. Oxidant stress and B vitamins status in patients with non-small cell lung cancer. Nutr Cancer. 2007;59:8–13.
pubmed: 17927496
doi: 10.1080/01635580701365043
Wikoff WR, Grapov D, Fahrmann JF, DeFelice B, Rom WN, Pass HI, et al. Metabolomic markers of altered nucleotide metabolism in early stage adenocarcinoma. Cancer Prev Res (Philos). 2015;8:410–8.
doi: 10.1158/1940-6207.CAPR-14-0329
Moreno P, Jimenez-Jimenez C, Garrido-Rodriguez M, Calderon-Santiago M, Molina S, Lara-Chica M, et al. Metabolomic profiling of human lung tumor tissues - nucleotide metabolism as a candidate for therapeutic interventions and biomarkers. Mol Oncol. 2018;12:1778–96.
pubmed: 30099851
pmcid: 6165994
doi: 10.1002/1878-0261.12369
Hu W, Wang G, Yarmus LB, Wan Y. Combined methylome and transcriptome analyses reveals potential therapeutic targets for EGFR wild type lung cancers with low PD-L1 expression. Cancers (Basel). 2020;12:2496.
doi: 10.3390/cancers12092496
Kijkog WE, BeIce A, Ozyyurt E, Tepeler Z. Xanthine oxidase levels in human brain tumors. Cancer Letters. 1990;50:179–81.
doi: 10.1016/0304-3835(90)90262-V
Rajaraman P, Brenner AV, Neta G, Pfeiffer R, Wang SS, Yeager M, et al. Risk of meningioma and common variation in genes related to innate immunity. Cancer Epidemiol Biomark Prev. 2010;19:1356–61.
doi: 10.1158/1055-9965.EPI-09-1151
Schulten H-J, Hussein D, Al-Adwani F, Karim S, Al-Maghrabi J, Al-Sharif M. Microarray expression profiling identifies genes, including cytokines, and biofunctions, as diapedesis, associated with a brain metastasis from a papillary thyroid carcinoma. Am J Cancer Res. 2016;6:2140–61.
pubmed: 27822408
pmcid: 5088282
Uzu M, Nonaka M, Miyano K, Sato H, Kurebayashi N, Yanagihara K, et al. A novel strategy for treatment of cancer cachexia targeting xanthine oxidase in the brain. J Pharmacol Sci. 2019;140:109–12.
pubmed: 31155393
doi: 10.1016/j.jphs.2019.04.005
Moloney JN, Cotter TG. ROS signalling in the biology of cancer. Semin Cell Dev Biol. 2018;80:50–64.
pubmed: 28587975
doi: 10.1016/j.semcdb.2017.05.023
Dumitrescu RG, Shields PG. The etiology of alcohol-induced breast cancer. Alcohol. 2005;35:213–25.
pubmed: 16054983
doi: 10.1016/j.alcohol.2005.04.005
Wright RM, Mcmanaman JL, Repine JE. Alcohol-induced breast cancer:a proposed mechanism. Free Radic Biol Med. 1999;26:348–54.
pubmed: 9895226
doi: 10.1016/S0891-5849(98)00204-4
Bir SC, Kolluru GK, Fang K, Kevil CG. Redox balance dynamically regulates vascular growth and remodeling. Semin Cell Dev Biol. 2012;23:745–57.
pubmed: 22634069
pmcid: 4041599
doi: 10.1016/j.semcdb.2012.05.003
Liu J, Wang C, Liu F, Lu Y, Cheng J. Metabonomics revealed xanthine oxidase-induced oxidative stress and inflammation in the pathogenesis of diabetic nephropathy. Anal Bioanal Chem. 2015;407:2569–79.
pubmed: 25636229
doi: 10.1007/s00216-015-8481-0
Lugrin J, Rosenblatt-Velin N, Parapanov R, Liaudet L. The role of oxidative stress during inflammatory processes. Biol Chem. 2014;395:203–30.
pubmed: 24127541
doi: 10.1515/hsz-2013-0241
Nanduri J, Vaddi DR, Khan SA, Wang N, Makarenko V, Semenza GL, et al. HIF-1alpha activation by intermittent hypoxia requires NADPH oxidase stimulation by xanthine oxidase. PLoS One. 2015;10:e0119762.
pubmed: 25751622
pmcid: 4353619
doi: 10.1371/journal.pone.0119762
Balamurugan K. HIF-1 at the crossroads of hypoxia, inflammation, and cancer. Int J Cancer. 2016;138:1058–66.
pubmed: 25784597
doi: 10.1002/ijc.29519
Griguer CE, Oliva CR, Kelley EE, Giles GI, Lancaster JR Jr, Gillespie GY. Xanthine oxidase-dependent regulation of hypoxia-inducible factor in cancer cells. Cancer Res. 2006;66:2257–63.
pubmed: 16489029
doi: 10.1158/0008-5472.CAN-05-3364
Shi DY, Xie FZ, Zhai C, Stern JS, Liu Y, Liu SL. The role of cellular oxidative stress in regulating glycolysis energy metabolism in hepatoma cells. Mol Cancer. 2009;8:32.
pubmed: 19497135
pmcid: 2702299
doi: 10.1186/1476-4598-8-32
Kusano T, Ehirchiou D, Matsumura T, Chobaz V, Nasi S, Castelblanco M, et al. Targeted knock-in mice expressing the oxidase-fixed form of xanthine oxidoreductase favor tumor growth. Nat Commun. 2019;10:4904.
pubmed: 31659168
pmcid: 6817904
doi: 10.1038/s41467-019-12565-z
Ives A, Nomura J, Martinon F, Roger T, LeRoy D, Miner JN, et al. Xanthine oxidoreductase regulates macrophage IL1beta secretion upon NLRP3 inflammasome activation. Nat Commun. 2015;6:6555.
pubmed: 25800347
doi: 10.1038/ncomms7555
Yim K, Bindayi A, McKay R, Mehrazin R, Raheem OA, Field C, et al. Rising serum uric acid level is negatively associated with survival in renal cell carcinoma. Cancers (Basel). 2019;11:536.
pmcid: 6520981
doi: 10.3390/cancers11040536
Yang S, He X, Liu Y, Ding X, Jiang H, Tan Y, et al. Prognostic significance of serum uric acid and gamma-glutamyltransferase in patients with advanced gastric cancer. Dis Markers. 2019;2019:1415421.
pubmed: 31885729
pmcid: 6918938
doi: 10.1155/2019/1415421
Chen YF, Li Q, Chen DT, Pan JH, Chen YH, Wen ZS, et al. Prognostic value of pre-operative serum uric acid levels in esophageal squamous cell carcinoma patients who undergo R0 esophagectomy. Cancer Biomark. 2016;17:89–96.
pubmed: 27314297
doi: 10.3233/CBM-160621
Stotz M, Szkandera J, Seidel J, Stojakovic T, Samonigg H, Reitz D, et al. Evaluation of uric acid as a prognostic blood-based marker in a large cohort of pancreatic cancer patients. PLoS One. 2014;9:e104730.
pubmed: 25133546
pmcid: 4136788
doi: 10.1371/journal.pone.0104730
Mao L, Guo C, Zheng S. Elevated urinary 8-oxo-7,8-dihydro-2’-deoxyguanosine and serum uric acid are associated with progression and are prognostic factors of colorectal cancer. Onco Targets Ther. 2018;11:5895–902.
pubmed: 30271173
pmcid: 6149868
doi: 10.2147/OTT.S175112
Chen CJ, Yen JH, Chang SJ. Gout patients have an increased risk of developing most cancers, especially urological cancers. Scand J Rheumatol. 2014;43:385–90.
pubmed: 24825466
doi: 10.3109/03009742.2013.878387
Sautin YY, Nakagawa T, Zharikov S, Johnson RJ. Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress. Am J Physiol Cell Physiol. 2007;293:C584–96.
pubmed: 17428837
doi: 10.1152/ajpcell.00600.2006
Yu M-A, Sánchez-Lozada LG, Johnson RJ, Kang D-H. Oxidative stress with an activation of the renin–angiotensin system in human vascular endothelial cells as a novel mechanism of uric acid-induced endothelial dysfunction. J Hyperts. 2010;28:1234–42.
doi: 10.1097/HJH.0b013e328337da1d
So A, Thorens B. Uric acid transport and disease. J Clin Invest. 2010;120:1791–9.
pubmed: 20516647
pmcid: 2877959
doi: 10.1172/JCI42344
Braga TT, Forni MF, Correa-Costa M, Ramos RN, Barbuto JA, Branco P, et al. Soluble uric acid activates the NLRP3 inflammasome. Sci Rep. 2017;7:39884.
pubmed: 28084303
pmcid: 5233987
doi: 10.1038/srep39884
Nakagawa T, Lanaspa MA, Millan IS, Fini M, Rivard CJ, Sanchez-Lozada LG, et al. Fructose contributes to the Warburg effect for cancer growth. Cancer Metab. 2020;8:16.
pubmed: 32670573
pmcid: 7350662
doi: 10.1186/s40170-020-00222-9
Johnson RJ, Nakagawa T, Sanchez-Lozada LG, Shafiu M, Sundaram S, Le M, et al. Sugar, uric acid, and the etiology of diabetes and obesity. Diabetes. 2013;62:3307–15.
pubmed: 24065788
pmcid: 3781481
doi: 10.2337/db12-1814
Lanaspa MA, Sanchez-Lozada LG, Choi YJ, Cicerchi C, Kanbay M, Roncal-Jimenez CA, et al. Uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress: potential role in fructose-dependent and -independent fatty liver. J Biol Chem. 2012;287:40732–44.
pubmed: 23035112
pmcid: 3504786
doi: 10.1074/jbc.M112.399899
Rock KL, Kataoka H, Lai JJ. Uric acid as a danger signal in gout and its comorbidities. Nat Rev Rheumatol. 2013;9:13–23.
pubmed: 22945591
doi: 10.1038/nrrheum.2012.143
Shi Y, Mucsi AD, Ng G. Monosodium urate crystals in inflammation and immunity. Immunol Rev. 2010;233:203–17.
pubmed: 20193001
doi: 10.1111/j.0105-2896.2009.00851.x
Bent R, Moll L, Grabbe S, Bros M. Interleukin-1 Beta-a friend or foe in malignancies? Int J Mol Sci. 2018;19:2155.
pmcid: 6121377
doi: 10.3390/ijms19082155
Rébé C, Ghiringhelli F. Interleukin-1β and cancer. Cancers. 2020;12:1791.
pmcid: 7408158
doi: 10.3390/cancers12071791
Jeong J, Rao AU, Xu J, Ogg SL, Hathout Y, Fenselau C, et al. The PRY/SPRY/B30.2 Domain of Butyrophilin 1A1 (BTN1A1) Binds to Xanthine Oxidoreductase: IMPLICATIONS FOR THE FUNCTION OF BTN1A1 IN THE MAMMARY GLAND AND OTHER TISSUES*. J Biol Chem. 2009;284:22444–56.
pubmed: 19531472
pmcid: 2755966
doi: 10.1074/jbc.M109.020446
Arnett HA, Viney JL. Immune modulation by butyrophilins. Nat Rev Immunol. 2014;14:559–69.
pubmed: 25060581
doi: 10.1038/nri3715
Smith IA, Knezevic BR, Ammann JU, Rhodes DA, Aw D, Palmer DB, et al. BTN1A1, the mammary gland butyrophilin, and BTN2A2 are both inhibitors of T cell activation. J Immunol. 2010;184:3514–25.
pubmed: 20208008
doi: 10.4049/jimmunol.0900416
LaRocca J, Pietruska J, Hixon M. Akt1 is essential for postnatal mammary gland development, function, and the expression of Btn1a1. PLoS One. 2011;6:e24432.
pubmed: 21915327
pmcid: 3168520
doi: 10.1371/journal.pone.0024432
Haddow A, Lamirande GDE, Bergel F, Bray RC, Gilbert DA. Anti-tumour and biochemical effects of purified bovine xanthine oxidase in C3H and C mice. Nature. 1958;182:1144–6.
pubmed: 13590253
doi: 10.1038/1821144a0
Bhat AH, Dar KB, Anees S, Zargar MA, Masood A, Sofi MA, et al. Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed Pharmacother. 2015;74:101–10.
pubmed: 26349970
doi: 10.1016/j.biopha.2015.07.025
Battelli MG, Musiani S, Tazzari PL, Stirpe F. Oxidative stress to human lymphocytes by xanthine oxidoreductase activity. Free Radic Res. 2001;35:665–79.
pubmed: 11811520
doi: 10.1080/10715760100301191
Xu H, Li C, Mozziconacci O, Zhu R, Xu Y, Tang Y, et al. Xanthine oxidase-mediated oxidative stress promotes cancer cell-specific apoptosis. Free Radic Biol Med. 2019;139:70–9.
pubmed: 31103463
pmcid: 6662189
doi: 10.1016/j.freeradbiomed.2019.05.019
Huang CC, Chen KL, Cheung CHA, Chang JY. Autophagy induced by cathepsin S inhibition induces early ROS production, oxidative DNA damage, and cell death via xanthine oxidase. Free Radic Biol Med. 2013;65:1473–86.
pubmed: 23892358
doi: 10.1016/j.freeradbiomed.2013.07.020
Fini MA, Orchard-Webb D, Kosmider B, Amon JD, Kelland R, Shibao G, et al. Migratory activity of human breast cancer cells is modulated by differential expression of xanthine oxidoreductase. J Cell Biochem. 2008;105:1008–26.
pubmed: 18767115
pmcid: 2587521
doi: 10.1002/jcb.21901
Tanhehco EJ, Yasojima K, Fau - McGeer PL, McGeer Pl, Fau - Washington RA, et al. Free radicals upregulate complement expression in rabbit isolated heart. Am J Physiol Heart Circ Physiol. 2000;279:H195–H201.
pubmed: 10899056
doi: 10.1152/ajpheart.2000.279.1.H195
Afshar-Kharghan V. The role of the complement system in cancer. J Clin Invest. 2017;127:780–9.
pubmed: 28248200
pmcid: 5330758
doi: 10.1172/JCI90962
Taghizadeh N, Vonk JM, Boezen HM. Serum uric acid levels and cancer mortality risk among males in a large general population-based cohort study. Cancer Causes Control. 2014;25:1075–80.
pubmed: 24906474
pmcid: 4082647
doi: 10.1007/s10552-014-0408-0
Kuhn T, Sookthai D, Graf ME, Schubel R, Freisling H, Johnson T, et al. Albumin, bilirubin, uric acid and cancer risk: results from a prospective population-based study. Br J Cancer. 2017;117:1572–9.
pubmed: 28898231
pmcid: 5680462
doi: 10.1038/bjc.2017.313
Benli E, Cirakoglu A, Ayyildiz SN, Yuce A. Comparison of serum uric acid levels between prostate cancer patients and a control group. Cent Eur J Urol. 2018;71:242–7.
Hsueh CY, Shao M, Cao W, Li S, Zhou L. Pretreatment serum uric acid as an efficient predictor of prognosis in men with laryngeal squamous cell cancer: a retrospective cohort study. Oxid Med Cell Longev. 2019;2019:1821969.
pubmed: 31178950
pmcid: 6501142
doi: 10.1155/2019/1821969
Yu R, Schellhorn HE. Recent applications of engineered animal antioxidant deficiency models in human nutrition and chronic disease. The J Nutr. 2013;143:1–11.
pubmed: 23173175
doi: 10.3945/jn.112.168690
Barros MP, Ganini D, Lorenço-Lima L, Soares CO, Pereira B, Bechara EJH, et al. Effects of acute creatine supplementation on iron homeostasis and uric acid-based antioxidant capacity of plasma after wingate test. J Int Soc Sports Nutr. 2012;9:25.
pubmed: 22691230
pmcid: 3439332
doi: 10.1186/1550-2783-9-25
Ames BN, Cathcart R, Schwiers E, Hochsteint P. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci USA. 1981;78:6858–62.
pubmed: 6947260
pmcid: 349151
doi: 10.1073/pnas.78.11.6858
Itahana Y, Han R, Barbier S, Lei Z, Rozen S, Itahana K. The uric acid transporter SLC2A9 is a direct target gene of the tumor suppressor p53 contributing to antioxidant defense. Oncogene. 2014;34:1799–810.
pubmed: 24858040
doi: 10.1038/onc.2014.119
Han X, Yang J, Li D, Guo Z. Overexpression of uric acid transporter SLC2A9 inhibits proliferation of hepatocellular carcinoma cells. Oncol Res. 2019;27:533–40.
pubmed: 29523220
pmcid: 7848443
doi: 10.3727/096504018X15199489058224
Shi Y, Evans JE, Rock KL. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature. 2003;425:516–21.
pubmed: 14520412
doi: 10.1038/nature01991
Jerome KR, Corey L. The danger within. N Engl J Med. 2004;350:411–2.
pubmed: 14736935
doi: 10.1056/NEJMcibr032455
Wang Y, Ma X, Su C, Peng B, Du J, Jia H, et al. Uric acid enhances the antitumor immunity of dendritic cell-based vaccine. Sci Rep. 2015;5:16427.
pubmed: 26553557
pmcid: 4639747
doi: 10.1038/srep16427
Furuhashi M. New insights into purine metabolism in metabolic diseases: role of xanthine oxidoreductase activity. Am J Physiol Endocrinol Metab. 2020;319:E827–E34.
pubmed: 32893671
doi: 10.1152/ajpendo.00378.2020
Yin J, Ren W, Huang X, Deng J, Li T, Yin Y. Potential mechanisms connecting purine metabolism and cancer therapy. Front Immunol. 2018;9:1697.
pubmed: 30105018
pmcid: 6077182
doi: 10.3389/fimmu.2018.01697
Townsend MH, Robison RA, O’Neill KL. A review of HPRT and its emerging role in cancer. Med Oncol. 2018;35:89.
pubmed: 29730818
doi: 10.1007/s12032-018-1144-1
Vickneson K, George J. Xanthine oxidoreductase inhibitors. Handb Exp Pharmacol. 2021;264:205–28.
pubmed: 32789757
doi: 10.1007/164_2020_383
Day RO, Graham GG, Hicks M, McLachlan AJ, Stocker SL, Williams KM. Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Clin Pharmacokinet. 2007;46:623–44.
pubmed: 17655371
doi: 10.2165/00003088-200746080-00001
Bardin T, Richette P. The role of febuxostat in gout. Curr Opin Rheumatol. 2019;31:152–8.
pubmed: 30601228
doi: 10.1097/BOR.0000000000000573
Frampton JE. Febuxostat: a review of its use in the treatment of hyperuricaemia in patients with gout. Drugs. 2015;75:427–38.
pubmed: 25724536
doi: 10.1007/s40265-015-0360-7
Matsumoto K, Okamoto K, Ashizawa N, Nishino T. FYX-051: a novel and potent hybrid-type inhibitor of xanthine oxidoreductase. J Pharmacol Exp Ther. 2011;336:95–103.
pubmed: 20952484
doi: 10.1124/jpet.110.174540
Luo Z, Yu G, Han X, Yang T, Ji Y, Huang H, et al. Prediction of the pharmacokinetics and pharmacodynamics of topiroxostat in humans by integrating the physiologically based pharmacokinetic model with the drug-target residence time model. Biomed Pharmacother. 2020;121:109660.
pubmed: 31733581
doi: 10.1016/j.biopha.2019.109660
Smelcerovic A, Tomovic K, Smelcerovic Z, Petronijevic Z, Kocic G, Tomasic T, et al. Xanthine oxidase inhibitors beyond allopurinol and febuxostat; an overview and selection of potential leads based on in silico calculated physico-chemical properties, predicted pharmacokinetics and toxicity. Eur J Med Chem. 2017;135:491–516.
pubmed: 28478180
doi: 10.1016/j.ejmech.2017.04.031
Baracos VE, Martin L, Korc M, Guttridge DC, Fearon KCH. Cancer-associated cachexia. Nat Rev Dis Prim. 2018;4:17105.
pubmed: 29345251
doi: 10.1038/nrdp.2017.105
Schmidt SF, Rohm M, Herzig S, Berriel, Diaz M. Cancer cachexia: more than skeletal muscle wasting. Trends Cancer. 2018;4:849–60.
pubmed: 30470306
doi: 10.1016/j.trecan.2018.10.001
Argiles JM, Busquets S, Stemmler B, Lopez-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14:754–62.
pubmed: 25291291
doi: 10.1038/nrc3829
Konishi M, Pelgrim L, Tschirner A, Baumgarten A, von Haehling S, Palus S, et al. Febuxostat improves outcome in a rat model of cancer cachexia. J Cachexia Sarcopenia Muscle. 2015;6:174–80.
pubmed: 26136193
pmcid: 4458083
doi: 10.1002/jcsm.12017
Alakel N, Middeke JM, Schetelig J, Bornhauser M. Prevention and treatment of tumor lysis syndrome, and the efficacy and role of rasburicase. Onco Targets Ther. 2017;10:597–605.
pubmed: 28203093
pmcid: 5295804
doi: 10.2147/OTT.S103864
Nicholaou T, Wong R, Davis ID. Tumour lysis syndrome in a patient with renal-cell carcinoma treated with sunitinib malate. Lancet. 2007;369:1923–4.
pubmed: 17560435
doi: 10.1016/S0140-6736(07)60903-9
Wilson FP, Berns JS. Tumor lysis syndrome: new challenges and recent advances. Adv Chronic Kidney Dis. 2014;21:18–26.
pubmed: 24359983
pmcid: 4017246
doi: 10.1053/j.ackd.2013.07.001
Sood AR, Burry LD. FCCP, Cheng DoretKF. Clarifying the role of Rasburicase in tumor lysis syndrome. Pharmacotherapy. 2007;27:111–21.
pubmed: 17192165
doi: 10.1592/phco.27.1.111
Stuckert AJ, Schafer ES, Bernhardt MB, Baxter P, Brackett J. Use of allopurinol to reduce hepatotoxicity from 6-mercaptopurine (6-MP) in patients with acute lymphoblastic leukemia (ALL). Leuk Lymphoma. 2020;61:1246–9.
pubmed: 31842647
doi: 10.1080/10428194.2019.1702183
Cohen G, Cooper S, Sison EA, Annesley C, Bhuiyan M, Brown P. Allopurinol use during pediatric acute lymphoblastic leukemia maintenance therapy safely corrects skewed 6-mercaptopurine metabolism, improving inadequate myelosuppression and reducing gastrointestinal toxicity. Pediatr Blood Cancer. 2020;67:e28360.
pubmed: 32909665
pmcid: 8773437
doi: 10.1002/pbc.28360
Tamura K, Kawai Y, Kiguchi T, Okamoto M, Kaneko M, Maemondo M, et al. Efficacy and safety of febuxostat for prevention of tumor lysis syndrome in patients with malignant tumors receiving chemotherapy: a phase III, randomized, multi-center trial comparing febuxostat and allopurinol. Int J Clin Oncol. 2016;21:996–1003.
pubmed: 27017611
doi: 10.1007/s10147-016-0971-3
Takai M, Yamauchi T, Ookura M, Matsuda Y, Tai K, Kishi S, et al. Febuxostat for management of tumor lysis syndrome including its effects on levels of purine metabolites in patients with hematological malignancies - a single institutio’s, pharmacokinetic and pilot prospective study. Anticancer Res. 2014;34:7287.
pubmed: 25503162
Shih HJ, Kao MC, Tsai PS, Fan YC, Huang CJ. Long-term allopurinol use decreases the risk of prostate cancer in patients with gout: a population-based study. Prostate Cancer Prostatic Dis. 2017;20:328–33.
pubmed: 28398294
doi: 10.1038/pcan.2017.14
Yasuda T, Yoshida T, Goda AE, Horinaka M, Yano K, Shiraishi T, et al. Anti-gout agent allopurinol exerts cytotoxicity to human hormone-refractory prostate cancer cells in combination with tumor necrosis factor-related apoptosis-inducing ligand. Mol Cancer Res. 2008;6:1852–60.
pubmed: 19074830
doi: 10.1158/1541-7786.MCR-08-0012
Tavassoly I, Hu Y, Zhao S, Mariottini C, Boran A, Chen Y, et al. Genomic signatures defining responsiveness to allopurinol and combination therapy for lung cancer identified by systems therapeutics analyses. Mol Oncol. 2019;13:1725–43.
pubmed: 31116490
pmcid: 6670022
doi: 10.1002/1878-0261.12521
Alfaifi MY, Shati AA, Elbehairi SEI, Fahmy UA, Alhakamy NA, Md S. Anti-tumor effect of PEG-coated PLGA nanoparticles of febuxostat on A549 non-small cell lung cancer cells. 3 Biotech. 2020;10:133.
pubmed: 32154046
pmcid: 7036082
doi: 10.1007/s13205-020-2077-x
Fahmy UA, Aldawsari HM, Badr-Eldin SM, Ahmed OAA, Alhakamy NA, Alsulimani HH, et al. The encapsulation of febuxostat into emulsomes strongly enhances the cytotoxic potential of the drug on HCT 116 colon cancer cells. Pharmaceutics. 2020;12:956.
pmcid: 7600960
doi: 10.3390/pharmaceutics12100956
Oh SH, Choi SY, Choi HJ, Ryu HM, Kim YJ, Jung HY, et al. The emerging role of xanthine oxidase inhibition for suppression of breast cancer cell migration and metastasis associated with hypercholesterolemia. FASEB J. 2019;33:7301–14.
pubmed: 30860872
doi: 10.1096/fj.201802415RR
Xu X, Rao G, Li Y. Xanthine oxidoreductase is required for genotoxic stressinduced NKG2D ligand expression and gemcitabine-mediated antitumor activity. Oncotarget. 2016;7:59220–35.
pubmed: 27494876
pmcid: 5312307
doi: 10.18632/oncotarget.11042
Zhou W, Yao Y, Scott AJ, Wilder-Romans K, Dresser JJ, Werner CK, et al. Purine metabolism regulates DNA repair and therapy resistance in glioblastoma. Nat Commun. 2020;11:3811.
pubmed: 32732914
pmcid: 7393131
doi: 10.1038/s41467-020-17512-x
Ma F, Zhu Y, Liu X, Zhou Q, Hong X, Qu C, et al. Dual-specificity tyrosine phosphorylation-regulated kinase 3 loss activates purine metabolism and promotes hepatocellular carcinoma progression. Hepatology. 2019;70:1785–803.
pubmed: 31066068
doi: 10.1002/hep.30703
Zhou Q, Lin M, Feng X, Ma F, Zhu Y, Liu X, et al. Targeting CLK3 inhibits the progression of cholangiocarcinoma by reprogramming nucleotide metabolism. J Exp Med. 2020;217:e20191779.
pubmed: 32453420
pmcid: 7398168
doi: 10.1084/jem.20191779
Lars Petter J, Laurent C. Therapeutic perspectives for cN-II in cancer. Curr Med Chem. 2013;20:4292–303.
doi: 10.2174/0929867311320340008
Furman RR, Hoelzer D. Purine nucleoside phosphorylase inhibition as a novel therapeutic approach for B-cell lymphoid malignancies. Semin Oncol. 2007;34:S29–34.
pubmed: 18086344
doi: 10.1053/j.seminoncol.2007.11.004