Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Mini Reviews in Medicinal Chemistry
  4. Volume 25, Issue 4
  5. Article
Volume 25, Issue 4
  • ISSN: 1389-5575
  • E-ISSN: 1875-5607

Abstract

Cuproptosis, an emerging concept in the field of diabetes research, presents a novel and promising perspective for the effective management of diabetes mellitus and its associated complications. Diabetes, characterized by chronic hyperglycemia, poses a substantial global health burden, with an increasing prevalence worldwide. Despite significant progress in our understanding of this complex metabolic disorder, optimal therapeutic strategies still remain elusive. The advent of cuproptosis, a term coined to describe copper-induced cellular cell death and its pivotal role in diabetes pathogenesis, opens new avenues for innovative interventions. Copper, an indispensable trace element, plays a pivotal role in a myriad of vital biological processes, encompassing energy production, bolstering antioxidant defenses, and altered cellular signaling. However, in the context of diabetes, this copper homeostasis is perturbed, driven by a combination of genetic predisposition, dietary patterns, and environmental factors. Excessive copper levels act as catalysts for oxidative stress, sparking intricate intracellular signaling cascades that further exacerbate metabolic dysfunction. In this review, we aim to explore the interrelationship between copper and diabetes comprehensively, shedding light on the intricate mechanisms underpinning cuproptosis. By unraveling the roles of copper transporters, copper-dependent enzymes, and cuproptotic signaling pathways, we seek to elucidate potential therapeutic strategies that harness the power of copper modulation in diabetes management. This insight sets the stage for a targeted approach to challenge the complex hurdles posed by diabetes, potentially transforming our therapeutic strategies in the ongoing fight against this pervasive global health concern.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/mrmc/10.2174/0113895575308206240911104945
2024-09-26
2025-04-13

  • From This Site

    /content/journals/mrmc/10.2174/0113895575308206240911104945
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. XieJ. YangY. GaoY. HeJ. Cuproptosis: Mechanisms and links with cancers.Mol. Cancer20232214610.1186/s12943‑023‑01732‑y 36882769
     [Google Scholar]
  2. GaoL. ZhangA. Copper-instigated modulatory cell mortality mechanisms and progress in oncological treatment investigations.Front. Immunol.202314123606310.3389/fimmu.2023.1236063 37600774
     [Google Scholar]
  3. HanJ. LuoJ. WangC. KapilevichL. ZhangX. Roles and mechanisms of copper homeostasis and cuproptosis in osteoarticular diseases.Biomed. Pharmacother.202417411657010.1016/j.biopha.2024.116570 38599063
     [Google Scholar]
  4. YangL. YangP. LipG.Y.H. RenJ. Copper homeostasis and cuproptosis in cardiovascular disease therapeutics.Trends Pharmacol. Sci.202344957358510.1016/j.tips.2023.07.004 37500296
     [Google Scholar]
  5. ProhaskaJ.R. Role of copper transporters in copper homeostasis.Am. J. Clin. Nutr.2008883826S829S10.1093/ajcn/88.3.826S 18779302
     [Google Scholar]
  6. CollinsJ.F. ProhaskaJ.R. KnutsonM.D. Metabolic crossroads of iron and copper.Nutr. Rev.201068313314710.1111/j.1753‑4887.2010.00271.x 20384844
     [Google Scholar]
  7. TapieroH. TownsendD.M. TewK.D. Trace elements in human physiology and pathology. Copper.Biomed. Pharmacother.200357938639810.1016/S0753‑3322(03)00012‑X 14652164
     [Google Scholar]
  8. LiY. Copper homeostasis: Emerging target for cancer treatment.IUBMB Life20207291900190810.1002/iub.2341 32599675
     [Google Scholar]
  9. LutsenkoS. Copper trafficking to the secretory pathway.Metallomics20168984085210.1039/C6MT00176A 27603756
     [Google Scholar]
  10. LutsenkoS. BhattacharjeeA. HubbardA.L. Copper handling machinery of the brain.Metallomics20102959660810.1039/c0mt00006j 21072351
     [Google Scholar]
  11. CsiszarK. Lysyl oxidases: A novel multifunctional amine oxidase family.Prog. Nucleic Acid Res. Mol. Biol.20017013210.1016/S0079‑6603(01)70012‑8 11642359
     [Google Scholar]
  12. LutsenkoS. LeShaneE.S. ShindeU. Biochemical basis of regulation of human copper-transporting ATPases.Arch. Biochem. Biophys.2007463213414810.1016/j.abb.2007.04.013 17562324
     [Google Scholar]
  13. HordyjewskaA. PopiołekŁ. KocotJ. The many face of copper in medicine and treatment.Biometals201427461162110.1007/s10534‑014‑9736‑5 24748564
     [Google Scholar]
  14. de RomañaD.L. OlivaresM. UauyR. ArayaM. Risks and benefits of copper in light of new insights of copper homeostasis.J. Trace Elem. Med. Biol.201125131310.1016/j.jtemb.2010.11.004 21342755
     [Google Scholar]
  15. ViktorínováA. TošerováE. KrižkoM. ĎuračkováZ. Altered metabolism of copper, zinc, and magnesium is associated with increased levels of glycated hemoglobin in patients with diabetes mellitus.Metabolism200958101477148210.1016/j.metabol.2009.04.035 19592053
     [Google Scholar]
  16. GongD. LuJ. ChenX. ReddyS. CrossmanD.J. Glyn-JonesS. ChoongY.S. KennedyJ. BarryB. ZhangS. ChanY.K. RuggieroK. PhillipsA.R.J. CooperG.J.S. A copper(II)-selective chelator ameliorates diabetes-evoked renal fibrosis and albuminuria, and suppresses pathogenic TGF-β activation in the kidneys of rats used as a model of diabetes.Diabetologia20085191741175110.1007/s00125‑008‑1088‑7 18636238
     [Google Scholar]
  17. OzcelikD. TuncdemirM. OzturkM. UzunH. Evaluation of trace elements and oxidative stress levels in the liver and kidney of streptozotocin-induced experimental diabetic rat model.Gen. Physiol. Biophys.201230435636310.4149/gpb_2011_04_356 22131317
     [Google Scholar]
  18. RazI. HaviviE. Influence of chronic diabetes on tissue and blood cells status of zinc, copper, and chromium in the rat.Diabetes Res.1988711923 3402163
     [Google Scholar]
  19. LoweJ. Taveira-da-SilvaR. Hilário-SouzaE. Dissecting copper homeostasis in diabetes mellitus.IUBMB Life201769425526210.1002/iub.1614 28276155
     [Google Scholar]
  20. ZhangS. LiuH. AmarsinghG.V. CheungC.C.H. HoglS. NarayananU. ZhangL. McHargS. XuJ. GongD. KennedyJ. BarryB. ChoongY.S. PhillipsA.R.J. CooperG.J.S. Diabetic cardiomyopathy is associated with defective myocellular copper regulation and both defects are rectified by divalent copper chelation.Cardiovasc. Diabetol.201413110010.1186/1475‑2840‑13‑100 24927960
     [Google Scholar]
  21. ItoS. FujitaH. NaritaT. YaginumaT. KawaradaY. KawagoeM. SugiyamaT. Urinary copper excretion in type 2 diabetic patients with nephropathy.Nephron J.200188430731210.1159/000046013 11474224
     [Google Scholar]
  22. CooperG.J.S. ChanY.K. DissanayakeA.M. LeahyF.E. KeoghG.F. FramptonC.M. GambleG.D. BruntonD.H. BakerJ.R. PoppittS.D. Demonstration of a hyperglycemia-driven pathogenic abnormality of copper homeostasis in diabetes and its reversibility by selective chelation: Quantitative comparisons between the biology of copper and eight other nutritionally essential elements in normal and diabetic individuals.Diabetes20055451468147610.2337/diabetes.54.5.1468 15855335
     [Google Scholar]
  23. QiuQ. ZhangF. ZhuW. WuJ. LiangM. Copper in diabetes mellitus: A meta-analysis and systematic review of plasma and serum studies.Biol. Trace Elem. Res.20171771536310.1007/s12011‑016‑0877‑y 27785738
     [Google Scholar]
  24. MasadA. HayesL. TabnerB.J. TurnbullS. CooperL.J. FullwoodN.J. GermanM.J. KametaniF. El-AgnafO.M.A. AllsopD. Copper‐mediated formation of hydrogen peroxide from the amylin peptide: A novel mechanism for degeneration of islet cells in type‐2 diabetes mellitus?FEBS Lett.2007581183489349310.1016/j.febslet.2007.06.061 17617411
     [Google Scholar]
  25. SarkarA. DashS. BarikB.K. MuttigiM.S. KedageV. ShettyJ.K. PrakashM. Copper and ceruloplasmin levels in relation to total thiols and GST in type 2 diabetes mellitus patients.Indian J. Clin. Biochem.2010251747610.1007/s12291‑010‑0015‑0 23105888
     [Google Scholar]
  26. NakaT. KanetoH. KatakamiN. MatsuokaT. HaradaA. YamasakiY. MatsuhisaM. ShimomuraI. Association of serum copper levels and glycemic control in patients with type 2 diabetes.Endocr. J.201360339339610.1507/endocrj.EJ12‑0342 23197044
     [Google Scholar]
  27. LiS. ZhangX. CuiX. ZhaoL. RongY. Comment on relationship of circulating copper level with gestational diabetes mellitus: A meta-analysis and systemic review.Biol. Trace Elem. Res.202220063039304010.1007/s12011‑021‑02856‑2 34435314
     [Google Scholar]
  28. LiP. YinJ. ZhuY. LiS. ChenS. SunT. ShanZ. WangJ. ShangQ. LiX. YangW. LiuL. Association between plasma concentration of copper and gestational diabetes mellitus.Clin. Nutr.20193862922292710.1016/j.clnu.2018.12.032 30661907
     [Google Scholar]
  29. LiJ. JiangY. XuT. ZhangY. XueJ. GaoX. YangX. WangX. JiaX. ChengW. JinS. Wilson disease with novel compound heterozygote mutations in the ATP7B gene presenting with severe diabetes.Diabetes Care20204361363136510.2337/dc19‑2033 32291276
     [Google Scholar]
  30. MuscogiuriG. SalmonA.B. Aguayo-MazzucatoC. LiM. BalasB. Guardado-MendozaR. GiaccariA. ReddickR.L. ReynaS.M. WeirG. DeFronzoR.A. Van RemmenH. MusiN. Genetic disruption of SOD1 gene causes glucose intolerance and impairs β-cell function.Diabetes201362124201420710.2337/db13‑0314 24009256
     [Google Scholar]
  31. TanakaA. KanetoH. MiyatsukaT. YamamotoK. YoshiuchiK. YamasakiY. ShimomuraI. MatsuokaT. MatsuhisaM. Role of copper ion in the pathogenesis of type 2 diabetes.Endocr. J.200956569970610.1507/endocrj.K09E‑051 19461160
     [Google Scholar]
  32. GembilloG. LabbozzettaV. GiuffridaA.E. PeritoreL. CalabreseV. SpinellaC. StancanelliM.R. SpallinoE. ViscontiL. SantoroD. Potential role of copper in diabetes and diabetic kidney disease.Metabolites20221311710.3390/metabo13010017 36676942
     [Google Scholar]
  33. HarrisE.D. Copper as a cofactor and regulator of copper,zinc superoxide dismutase.J. Nutr.19921223Suppl.63664010.1093/jn/122.suppl_3.636 1542024
     [Google Scholar]
  34. KaziT.G. AfridiH.I. KaziN. JamaliM.K. ArainM.B. JalbaniN. KandhroG.A. Copper, chromium, manganese, iron, nickel, and zinc levels in biological samples of diabetes mellitus patients.Biol. Trace Elem. Res.2008122111810.1007/s12011‑007‑8062‑y 18193174
     [Google Scholar]
  35. EatonJ.W. QianM. Interactions of copper with glycated proteins: possible involvement in the etiology of diabetic neuropathy.Mol. Cell. Biochem.2002234/235113514210.1023/A:1015988817587 12162426
     [Google Scholar]
  36. KhanA.R. AwanF.R. Metals in the pathogenesis of type 2 diabetes.J. Diabetes Metab. Disord.20141311610.1186/2251‑6581‑13‑16 24401367
     [Google Scholar]
  37. GuestP.C. PipeleersD. RossierJ. RhodesC.J. HuttonJ.C. Co-secretion of carboxypeptidase H and insulin from isolated rat islets of Langerhans.Biochem. J.1989264250350810.1042/bj2640503 2481446
     [Google Scholar]
  38. ZhangY.M. ZimmerM.A. GuardiaT. CallahanS.J. MondalC. Di MartinoJ. TakagiT. FennellM. GarippaR. CampbellN.R. Bravo-CorderoJ.J. WhiteR.M. Distant insulin signaling regulates vertebrate pigmentation through the sheddase Bace2.Dev. Cell2018455580594.e710.1016/j.devcel.2018.04.025 29804876
     [Google Scholar]
  39. SunZ. ShaoY. YanK. YaoT. LiuL. SunF. WuJ. HuangY. The link between trace metal elements and glucose metabolism: Evidence from zinc, copper, iron, and manganese-mediated metabolic regulation.Metabolites20231310104810.3390/metabo13101048 37887373
     [Google Scholar]
  40. CaturanoA. D’AngeloM. MormoneA. RussoV. MollicaM.P. SalvatoreT. GalieroR. RinaldiL. VetranoE. MarfellaR. MondaM. GiordanoA. SassoF.C. Oxidative stress in type 2 diabetes: impacts from pathogenesis to lifestyle modifications.Curr. Issues Mol. Biol.20234586651666610.3390/cimb45080420 37623239
     [Google Scholar]
  41. SatyanarayanaG. KeishamN. BatraH.S. vS.M. KhanM. GuptaS. MahindraV. Evaluation of serum ceruloplasmin levels as a biomarker for oxidative stress in patients with diabetic retinopathy.Cureus2021132e1307010.7759/cureus.13070 33680612
     [Google Scholar]
  42. ImlayJ.A. ChinS.M. LinnS. Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro.Science1988240485264064210.1126/science.2834821 2834821
     [Google Scholar]
  43. CheM. WangR. LiX. WangH.Y. ZhengX.F.S. Expanding roles of superoxide dismutases in cell regulation and cancer.Drug Discov. Today201621114314910.1016/j.drudis.2015.10.001 26475962
     [Google Scholar]
  44. NithyaK. AngelineT. IsabelW. AsirvathamA.J. SOD1 Gene +35A/C (exon3/intron3) Polymorphism in Type 2 Diabetes Mellitus among South Indian Population.Genet. Res. Int.201620161510.1155/2016/3787268 27190652
     [Google Scholar]
  45. LynchS.M. ColónW. Dominant role of copper in the kinetic stability of Cu/Zn superoxide dismutase.Biochem. Biophys. Res. Commun.2006340245746110.1016/j.bbrc.2005.12.024 16375856
     [Google Scholar]
  46. LiuY. MiaoJ. An emerging role of defective copper metabolism in heart disease.Nutrients202214370010.3390/nu14030700 35277059
     [Google Scholar]
  47. HurrleS. HsuW.H. The etiology of oxidative stress in insulin resistance.Biomed. J.201740525726210.1016/j.bj.2017.06.007 29179880
     [Google Scholar]
  48. DrewsG. Krippeit-DrewsP. DüferM. Oxidative stress and beta-cell dysfunction.Pflugers Arch.2010460470371810.1007/s00424‑010‑0862‑9 20652307
     [Google Scholar]
  49. KashiharaN. HarunaY. KondetiV.K. KanwarY.S. Oxidative stress in diabetic nephropathy.Curr. Med. Chem.201017344256426910.2174/092986710793348581 20939814
     [Google Scholar]
  50. KowluruR.A. ChanP.S. Oxidative stress and diabetic retinopathy.J. Diabetes Res.20072007104360310.1155/2007/43603 17641741
     [Google Scholar]
  51. HosseiniA. AbdollahiM. Diabetic neuropathy and oxidative stress: Therapeutic perspectives.Oxid. Med. Cell. Longev.2013201311510.1155/2013/168039 23738033
     [Google Scholar]
  52. LiuZ. WangM. ZhangC. ZhouS. JiG. Molecular functions of ceruloplasmin in metabolic disease pathology.Diabetes Metab. Syndr. Obes.20221569571110.2147/DMSO.S346648 35264864
     [Google Scholar]
  53. HellmanN.E. GitlinJ.D. Ceruloplasmin metabolism and function.Annu. Rev. Nutr.200222143945810.1146/annurev.nutr.22.012502.114457 12055353
     [Google Scholar]
  54. ChackoS.K. CheluvappaR. Increased ceruloplasmin and fibrinogen in type 2 diabetes corresponds to decreased anti-oxidant activity in a preliminary tertiary South Indian hospital study.Exp. Clin. Endocrinol. Diabetes20101181646710.1055/s‑0029‑1225647 19834873
     [Google Scholar]
  55. RusticeanuM. ZimmerV. SchleithoffL. WonneyK. VieraJ. ZimmerA. HübschenU. BohleR.M. GrünhageF. LammertF. Novel ceruloplasmin mutation causing aceruloplasminemia with hepatic iron overload and diabetes without neurological symptoms.Clin. Genet.201485330030110.1111/cge.12145 23557349
     [Google Scholar]
  56. ZhangB. BurkeR. Copper homeostasis and the ubiquitin proteasome system.Metallomics2023153mfad01010.1093/mtomcs/mfad010 36822629
     [Google Scholar]
  57. RaoR.V. BredesenD.E. Misfolded proteins, endoplasmic reticulum stress and neurodegeneration.Curr. Opin. Cell Biol.200416665366210.1016/j.ceb.2004.09.012 15530777
     [Google Scholar]
  58. YangY. FengQ. LuanY. LiuH. JiaoY. HaoH. YuB. LuanY. RenK. Exploring cuproptosis as a mechanism and potential intervention target in cardiovascular diseases.Front. Pharmacol.202314122929710.3389/fphar.2023.1229297 37637426
     [Google Scholar]
  59. DuarteI.F. CaioJ. MoedasM.F. RodriguesL.A. LeandroA.P. RiveraI.A. SilvaM.F.B. Dihydrolipoamide dehydrogenase, pyruvate oxidation, and acetylation-dependent mechanisms intersecting drug iatrogenesis.Cell. Mol. Life Sci.202178237451746810.1007/s00018‑021‑03996‑3 34718827
     [Google Scholar]
  60. TsvetkovP. CoyS. PetrovaB. DreishpoonM. VermaA. AbdusamadM. RossenJ. Joesch-CohenL. HumeidiR. SpanglerR.D. EatonJ.K. FrenkelE. KocakM. CorselloS.M. LutsenkoS. KanarekN. SantagataS. GolubT.R. Copper induces cell death by targeting lipoylated TCA cycle proteins.Science202237565861254126110.1126/science.abf0529 35298263
     [Google Scholar]
  61. TianZ. JiangS. ZhouJ. ZhangW. Copper homeostasis and cuproptosis in mitochondria.Life Sci.202333412222310.1016/j.lfs.2023.122223 38084674
     [Google Scholar]
  62. TongX. TangR. XiaoM. XuJ. WangW. ZhangB. LiuJ. YuX. ShiS. Targeting cell death pathways for cancer therapy: Recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research.J. Hematol. Oncol.202215117410.1186/s13045‑022‑01392‑3 36482419
     [Google Scholar]
  63. GhemrawiR. KhairM. Endoplasmic reticulum stress and unfolded protein response in neurodegenerative diseases.Int. J. Mol. Sci.20202117612710.3390/ijms21176127 32854418
     [Google Scholar]
  64. OeS. MiyagawaK. HonmaY. HaradaM. Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease.Exp. Cell Res.2016347119220010.1016/j.yexcr.2016.08.003 27502587
     [Google Scholar]
  65. JiP. WangP. ChenH. XuY. GeJ. TianZ. YanZ. Potential of copper and copper compounds for anticancer applications.Pharmaceuticals (Basel)202316223410.3390/ph16020234 37259382
     [Google Scholar]
  66. GromadzkaG. TarnackaB. FlagaA. AdamczykA. Copper dyshomeostasis in neurodegenerative diseases—Therapeutic implications.Int. J. Mol. Sci.20202123925910.3390/ijms21239259 33291628
     [Google Scholar]
  67. SquittiR. SimonelliI. VentrigliaM. SiottoM. PasqualettiP. RembachA. DoeckeJ. BushA.I. Meta-analysis of serum non-ceruloplasmin copper in Alzheimer’s disease.J. Alzheimers Dis.201338480982210.3233/JAD‑131247 24072069
     [Google Scholar]
  68. SquittiR. LupoiD. PasqualettiP. Dal FornoG. VernieriF. ChiovendaP. RossiL. CortesiM. CassettaE. RossiniP.M. Elevation of serum copper levels in Alzheimer’s disease.Neurology20025981153116110.1212/WNL.59.8.1153 12391342
     [Google Scholar]
  69. BucossiS. VentrigliaM. PanettaV. SalustriC. PasqualettiP. MarianiS. SiottoM. RossiniP.M. SquittiR. Copper in Alzheimer’s disease: A meta-analysis of serum,plasma, and cerebrospinal fluid studies.J. Alzheimers Dis.201124117518510.3233/JAD‑2010‑101473 21187586
     [Google Scholar]
  70. TiwariA. LibaA. SohnS.H. SeetharamanS.V. BilselO. MatthewsC.R. HartP.J. ValentineJ.S. HaywardL.J. Metal deficiency increases aberrant hydrophobicity of mutant superoxide dismutases that cause amyotrophic lateral sclerosis.J. Biol. Chem.200928440277462775810.1074/jbc.M109.043729 19651777
     [Google Scholar]
  71. PrattA.J. ShinD.S. MerzG.E. RamboR.P. LancasterW.A. DyerK.N. BorbatP.P. PooleF.L.II AdamsM.W.W. FreedJ.H. CraneB.R. TainerJ.A. GetzoffE.D. Aggregation propensities of superoxide dismutase G93 hotspot mutants mirror ALS clinical phenotypes.Proc. Natl. Acad. Sci. USA201411143E4568E457610.1073/pnas.1308531111 25316790
     [Google Scholar]
  72. BourassaM.W. BrownH.H. BorcheltD.R. VogtS. MillerL.M. Metal-deficient aggregates and diminished copper found in cells expressing SOD1 mutations that cause ALS.Front. Aging Neurosci.2014611010.3389/fnagi.2014.00110 24982630
     [Google Scholar]
  73. TokudaE. OkawaE. OnoS. Dysregulation of intracellular copper trafficking pathway in a mouse model of mutant copper/zinc superoxide dismutase‐linked familial amyotrophic lateral sclerosis.J. Neurochem.2009111118119110.1111/j.1471‑4159.2009.06310.x 19656261
     [Google Scholar]
  74. EngeT.G. EcroydH. JolleyD.F. YerburyJ.J. DossetoA. Longitudinal assessment of metal concentrations and copper isotope ratios in the G93A SOD1 mouse model of amyotrophic lateral sclerosis.Metallomics20179216117410.1039/C6MT00270F 28067393
     [Google Scholar]
  75. RoosP.M. VesterbergO. SyversenT. FlatenT.P. NordbergM. Metal concentrations in cerebrospinal fluid and blood plasma from patients with amyotrophic lateral sclerosis.Biol. Trace Elem. Res.2013151215917010.1007/s12011‑012‑9547‑x 23225075
     [Google Scholar]
  76. DexterD.T. CarayonA. Javoy-AgidF. AgidY. WellsF.R. DanielS.E. LeesA.J. JennerP. MarsdenC.D. Alterations in the levels of iron, ferritin and other trace metals in Parkinson’s disease and other neurodegenerative diseases affecting the basal ganglia.Brain199111441953197510.1093/brain/114.4.1953 1832073
     [Google Scholar]
  77. FoxJ.H. KamaJ.A. LiebermanG. ChopraR. DorseyK. ChopraV. VolitakisI. ChernyR.A. BushA.I. HerschS. Mechanisms of copper ion mediated Huntington’s disease progression.PLoS One200723e33410.1371/journal.pone.0000334 17396163
     [Google Scholar]
  78. PavithraV. SathishaT.G. KasturiK. MallikaD.S. AmosS.J. RagunathaS. Serum levels of metal ions in female patients with breast cancer.J. Clin. Diagn. Res.201591BC25c2710.7860/JCDR/2015/11627.5476 25737978
     [Google Scholar]
  79. FengJ.F. LuL. ZengP. YangY.H. LuoJ. YangY.W. WangD. Serum total oxidant/antioxidant status and trace element levels in breast cancer patients.Int. J. Clin. Oncol.201217657558310.1007/s10147‑011‑0327‑y 21968912
     [Google Scholar]
  80. NayakS.B. BhatV.R. UpadhyayD. UdupaS.L. Copper and ceruloplasmin status in serum of prostate and colon cancer patients.Indian J. Physiol. Pharmacol.2003471108110 12708132
     [Google Scholar]
  81. MortazaviH. SabourS. BaharvandM. ManifarS. AkkafanR. Serum levels of ferritin, copper, and zinc in patients with oral cancer.Biomed. J.201437533133610.4103/2319‑4170.132888 25179706
     [Google Scholar]
  82. ShenF. CaiW.S. LiJ.L. FengZ. CaoJ. XuB. The association between serum levels of selenium, copper, and magnesium with thyroid cancer: A meta-analysis.Biol. Trace Elem. Res.2015167222523510.1007/s12011‑015‑0304‑9 25820485
     [Google Scholar]
  83. BasuS. SinghM.K. SinghT.B. BhartiyaS.K. SinghS.P. ShuklaV.K. Heavy and trace metals in carcinoma of the gallbladder.World J. Surg.201337112641264610.1007/s00268‑013‑2164‑9 23942528
     [Google Scholar]
  84. MargaliothE.J. SchenkerJ.G. ChevionM. Copper and zinc levels in normal and malignant tissues.Cancer198352586887210.1002/1097‑0142(19830901)52:5<868::AID‑CNCR2820520521>3.0.CO;2‑K 6871828
     [Google Scholar]
  85. YamanM. KayaG. SimsekM. Comparison of trace element concentrations in cancerous and noncancerous human endometrial and ovary tissues.Int. J. Gynecol. Cancer200717122022810.1111/j.1525‑1438.2006.00742.x 17291257
     [Google Scholar]
  86. LenerM.R. ScottR.J. Wiechowska-KozłowskaA. Serrano-FernándezP. BaszukP. Jaworska-BieniekK. SukiennickiG. MarciniakW. MuszyńskaM. KładnyJ. GromowskiT. KaczmarekK. JakubowskaA. LubińskiJ. Serum concentrations of selenium and copper in patients diagnosed with pancreatic cancer.Cancer Res. Treat.20164831056106410.4143/crt.2015.282 26727715
     [Google Scholar]
  87. SalehS.A.K. AdlyH.M. AbdelkhaliqA.A. NassirA.M. Serum levels of selenium, zinc, copper, manganese, and iron in prostate cancer patients.Curr. Urol.2020141444910.1159/000499261 32398996
     [Google Scholar]
  88. GuptaS.K. ShuklaV.K. VaidyaM.P. RoyS.K. GuptaS. Serum and tissue trace elements in colorectal cancer.J. Surg. Oncol.199352317217510.1002/jso.2930520311 8441275
     [Google Scholar]
  89. DíezM. ArroyoM. CerdànF.J. MuñozM. MartinM.A. BalibreaJ.L. Serum and tissue trace metal levels in lung cancer.Oncology198946423023410.1159/000226722 2740065
     [Google Scholar]
  90. SharmaK. MittalD.K. KesarwaniR.C. KambojV.P. Chowdhery. Diagnostic and prognostic significance of serum and tissue trace elements in breast malignancy.Indian J. Med. Sci.19944810227232 7829172
     [Google Scholar]
  91. ChenX. CaiQ. LiangR. ZhangD. LiuX. ZhangM. XiongY. XuM. LiuQ. LiP. YuP. ShiA. Copper homeostasis and copper-induced cell death in the pathogenesis of cardiovascular disease and therapeutic strategies.Cell Death Dis.202314210510.1038/s41419‑023‑05639‑w 36774340
     [Google Scholar]
  92. FordE.S. Serum copper concentration and coronary heart disease among US adults.Am. J. Epidemiol.2000151121182118810.1093/oxfordjournals.aje.a010168 10905530
     [Google Scholar]
  93. KokF.J. Van DuijnC.M. HofmanA. Van Der VoetG.B. De WolffF.A. PaaysC.H.C. ValkenburgH.A. Serum copper and zinc and the risk of death from cancer and cardiovascular disease.Am. J. Epidemiol.1988128235235910.1093/oxfordjournals.aje.a114975 3394701
     [Google Scholar]
  94. MedeirosD.M. WildmanR.E.C. Newer findings on a unified perspective of copper restriction and cardiomyopathy.Exp. Biol. Med. (Maywood)1997215429931310.3181/00379727‑215‑44141 9270715
     [Google Scholar]
  95. DiNicolantonioJ.J. ManganD. O’KeefeJ.H. Copper deficiency may be a leading cause of ischaemic heart disease.Open Heart201852e00078410.1136/openhrt‑2018‑000784 30364437
     [Google Scholar]
  96. KangY.J. WuH. SaariJ.T. Alterations in hypertrophic gene expression by dietary copper restriction in mouse heart.Proc. Soc. Exp. Biol. Med.20002233282287 10719841
     [Google Scholar]
  97. ChenL. MinJ. WangF. Copper homeostasis and cuproptosis in health and disease.Signal Transduct. Target. Ther.20227137810.1038/s41392‑022‑01229‑y 36414625
     [Google Scholar]
  98. KeD. ZhangZ. LiuJ. ChenP. LiJ. SunX. ChuY. LiL. Ferroptosis, necroptosis and cuproptosis: Novel forms of regulated cell death in diabetic cardiomyopathy.Front. Cardiovasc. Med.202310113572310.3389/fcvm.2023.1135723 36970345
     [Google Scholar]
  99. Uriu-AdamsJ.Y. KeenC.L. Copper, oxidative stress, and human health.Mol. Aspects Med.2005264-526829810.1016/j.mam.2005.07.015 16112185
     [Google Scholar]
  100. ZouY. WuS. XuX. TanX. YangS. ChenT. ZhangJ. LiS. LiW. WangF. Cope with copper: From molecular mechanisms of cuproptosis to copper-related kidney diseases.Int. Immunopharmacol.202413311207510.1016/j.intimp.2024.112075 38663316
     [Google Scholar]
  101. ChangW. LiP. Copper and Diabetes: Current Research and Prospect.Mol. Nutr. Food Res.20236723230046810.1002/mnfr.202300468 37863813
     [Google Scholar]
  102. MW HasanatoR. Trace elements in type 2 diabetes mellitus and their association with glycemic control.Afr. Health Sci.202020128729310.4314/ahs.v20i1.34 33402917
     [Google Scholar]
  103. SiddiquiK. BawazeerN. Scaria JoyS. Variation in macro and trace elements in progression of type 2 diabetes.ScientificWorldJournal201420141910.1155/2014/461591 25162051
     [Google Scholar]
  104. ZhengY. LiX.K. WangY. CaiL. The role of zinc, copper and iron in the pathogenesis of diabetes and diabetic complications: therapeutic effects by chelators.Hemoglobin2008321-213514510.1080/03630260701727077 18274991
     [Google Scholar]
  105. CooperG.J.S. Therapeutic potential of copper chelation with triethylenetetramine in managing diabetes mellitus and Alzheimer’s disease.Drugs201171101281132010.2165/11591370‑000000000‑00000 21770477
     [Google Scholar]
  106. CooperG.J. Selective divalent copper chelation for the treatment of diabetes mellitus.Curr. Med. Chem.201219172828286010.2174/092986712800609715 22455587
     [Google Scholar]
  107. CooperG.J.S. PhillipsA.R.J. ChoongS.Y. LeonardB.L. CrossmanD.J. BruntonD.H. SaafiL. DissanayakeA.M. CowanB.R. YoungA.A. OccleshawC.J. ChanY.K. LeahyF.E. KeoghG.F. GambleG.D. AllenG.R. PopeA.J. BoydP.D.W. PoppittS.D. BorgT.K. DoughtyR.N. BakerJ.R. Regeneration of the heart in diabetes by selective copper chelation.Diabetes20045392501250810.2337/diabetes.53.9.2501 15331567
     [Google Scholar]
  108. JülligM. ChenX. HickeyA.J. CrossmanD.J. XuA. WangY. GreenwoodD.R. ChoongY.S. SchönbergerS.J. MiddleditchM.J. PhillipsA.R.J. CooperG.J.S. Reversal of diabetes‐evoked changes in mitochondrial protein expression of cardiac left ventricle by treatment with a copper(II)‐selective chelator.Proteomics Clin. Appl.20071438739910.1002/prca.200600770 21136691
     [Google Scholar]
  109. LuJ. GongD. ChoongS.Y. XuH. ChanY-K. ChenX. FitzpatrickS. Glyn-JonesS. ZhangS. NakamuraT. RuggieroK. ObolonkinV. PoppittS.D. PhillipsA.R.J. CooperG.J.S. Copper(II)-selective chelation improves function and antioxidant defences in cardiovascular tissues of rats as a model of diabetes: Comparisons between triethylenetetramine and three less copper-selective transition-metal-targeted treatments.Diabetologia20105361217122610.1007/s00125‑010‑1698‑8 20221822
     [Google Scholar]
  110. PolishchukE.V. ConcilliM. IacobacciS. ChesiG. PastoreN. PiccoloP. PaladinoS. BaldantoniD. van IJzendoornS.C.D. ChanJ. ChangC.J. AmoresanoA. PaneF. PucciP. TaralloA. ParentiG. Brunetti-PierriN. SettembreC. BallabioA. PolishchukR.S. Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis.Dev. Cell201429668670010.1016/j.devcel.2014.04.033 24909901
     [Google Scholar]
  111. SudhaharV. UraoN. OshikawaJ. McKinneyR.D. LlanosR.M. MercerJ.F.B. Ushio-FukaiM. FukaiT. Copper transporter ATP7A protects against endothelial dysfunction in type 1 diabetic mice by regulating extracellular superoxide dismutase.Diabetes201362113839385010.2337/db12‑1228 23884884
     [Google Scholar]
  112. Hilário-SouzaE. CuillelM. MintzE. CharbonnierP. VieyraA. CassioD. LoweJ. Modulation of hepatic copper-ATPase activity by insulin and glucagon involves protein kinase A (PKA) signaling pathway.Biochim. Biophys. Acta Mol. Basis Dis.20161862112086209710.1016/j.bbadis.2016.08.008 27523629
     [Google Scholar]
  113. HuoS. WangQ. ShiW. PengL. JiangY. ZhuM. GuoJ. PengD. WangM. MenL. HuangB. LvJ. LinL. ATF3/SPI1/SLC31A1 signaling promotes cuproptosis induced by advanced glycosylation end products in diabetic myocardial injury.Int. J. Mol. Sci.2023242166710.3390/ijms24021667 36675183
     [Google Scholar]
  114. Sanchez-RangelE. InzucchiS.E. Metformin: Clinical use in type 2 diabetes.Diabetologia20176091586159310.1007/s00125‑017‑4336‑x 28770321
     [Google Scholar]
  115. PryorR. CabreiroF. Repurposing metformin: An old drug with new tricks in its binding pockets.Biochem. J.2015471330732210.1042/BJ20150497 26475449
     [Google Scholar]
  116. FujitaY. InagakiN. Metformin: Clinical topics and new mechanisms of action.Diabetol. Int.2017814610.1007/s13340‑016‑0300‑0 30603300
     [Google Scholar]
  117. MusiN. HirshmanM.F. NygrenJ. SvanfeldtM. BavenholmP. RooyackersO. ZhouG. WilliamsonJ.M. LjunqvistO. EfendicS. MollerD.E. ThorellA. GoodyearL.J. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes.Diabetes20025172074208110.2337/diabetes.51.7.2074 12086935
     [Google Scholar]
  118. KharechkinaE.S. NikiforovaA.B. BelosludtsevK.N. RokitskayaT.I. AntonenkoY.N. KruglovA.G. Pioglitazone is a mild carrier-dependent uncoupler of oxidative phosphorylation and a modulator of mitochondrial permeability transition.Pharmaceuticals (Basel)20211410104510.3390/ph14101045 34681269
     [Google Scholar]
  119. BogackaI. XieH. BrayG.A. SmithS.R. Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo.Diabetes20055451392139910.2337/diabetes.54.5.1392 15855325
     [Google Scholar]
  120. ApostolovaN. IannantuoniF. GruevskaA. MuntaneJ. RochaM. VictorV.M. Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions.Redox Biol.20203410151710.1016/j.redox.2020.101517 32535544
     [Google Scholar]
  121. QuanX. UddinR. HeiskanenA. ParmviM. NilsonK. DonolatoM. HansenM.F. RenaG. BoisenA. The copper binding properties of metformin – QCM-D, XPS and nanobead agglomeration.Chem. Commun. (Camb.)20155197173131731610.1039/C5CC04321B 26462973
     [Google Scholar]
  122. WinterW. DeJonghJ. PostT. PloegerB. UrquhartR. MoulesI. EcklandD. DanhofM. A mechanism-based disease progression model for comparison of long-term effects of pioglitazone, metformin and gliclazide on disease processes underlying Type 2 diabetes mellitus.J. Pharmacokinet. Pharmacodyn.200633331334310.1007/s10928‑006‑9008‑2 16552630
     [Google Scholar]
  123. MohibiS. ZhangY. PerngV. ChenM. ZhangJ. ChenX. Ferredoxin 1 is essential for embryonic development and lipid homeostasis.eLife202413e9165610.7554/eLife.91656 38251655
     [Google Scholar]
  124. DreishpoonM.B. FDX1 regulates cellular protein lipoylation through direct binding to LIAS.bioRxiv2023, 20232023.02.03.52647210.1101/2023.02.03.526472
     [Google Scholar]
  125. TangX. YanZ. MiaoY. HaW. LiZ. YangL. MiD. Copper in cancer: From limiting nutrient to therapeutic target.Front. Oncol.202313120915610.3389/fonc.2023.1209156 37427098
     [Google Scholar]
  126. ZulkifliM. SpelbringA.N. ZhangY. SomaS. ChenS. LiL. LeT. ShanbhagV. PetrisM.J. ChenT.Y. RalleM. BarondeauD.P. GohilV.M. FDX1-dependent and independent mechanisms of elesclomol-mediated intracellular copper delivery.Proc. Natl. Acad. Sci. USA202312010e221672212010.1073/pnas.2216722120 36848556
     [Google Scholar]
  127. LuH. LiangJ. HeX. YeH. RuanC. ShaoH. ZhangR. LiY. A novel oncogenic role of fdx1 in human melanoma related to pd-l1 immune checkpoint.Int. J. Mol. Sci.20232411918210.3390/ijms24119182 37298135
     [Google Scholar]
  128. QuJ. WangY. WangQ. Cuproptosis: Potential new direction in diabetes research and treatment.Front. Endocrinol. (Lausanne)202415134472910.3389/fendo.2024.1344729 38904034
     [Google Scholar]
  129. ShenJ. SanW. ZhengY. ZhangS. CaoD. ChenY. MengG. Different types of cell death in diabetic endothelial dysfunction.Biomed. Pharmacother.202316811580210.1016/j.biopha.2023.115802 37918258
     [Google Scholar]
  130. ChenY. LiaoL. WangB. WuZ. Identification and validation of immune and cuproptosis - Related genes for diabetic nephropathy by WGCNA and machine learning.Front. Immunol.202415133227910.3389/fimmu.2024.1332279 38390317
     [Google Scholar]
  131. SongJ. ZhuK. WangH. WuM. WuY. ZhangQ. Deciphering the emerging role of programmed cell death in diabetic wound healing.Int. J. Biol. Sci.202319154989500310.7150/ijbs.88461 37781514
     [Google Scholar]
  132. CuiX. WangY. LiuH. ShiM. WangJ. WangY. The molecular mechanisms of defective copper metabolism in diabetic cardiomyopathy.Oxid. Med. Cell. Longev.2022202211610.1155/2022/5418376 36238639
     [Google Scholar]
  133. FengD. ZhaoY. LiW. LiX. WanJ. WangF. Copper neurotoxicity: Induction of cognitive dysfunction: A review.Medicine (Baltimore)202310248e3637510.1097/MD.0000000000036375 38050287
     [Google Scholar]
  134. ChenJ. YangX. LiW. LinY. LinR. CaiX. YanB. XieB. LiJ. Potential molecular and cellular mechanisms of the effects of cuproptosis-related genes in the cardiomyocytes of patients with diabetic heart failure: A bioinformatics analysis.Front. Endocrinol. (Lausanne)202415137038710.3389/fendo.2024.1370387 38883603
     [Google Scholar]
  135. CaiL. TanY. HollandB. WintergerstK. Diabetic Cardiomyopathy and cell death: Focus on metal-mediated cell death.Cardiovasc. Toxicol.2024242718410.1007/s12012‑024‑09836‑7 38321349
     [Google Scholar]
  136. YiW.J. YuanY. BaoQ. ZhaoZ. DingH.S. SongJ. Analyzing immune cell infiltration and copper metabolism in diabetic foot ulcers.J. Inflamm. Res.2024173143315710.2147/JIR.S452609 38774446
     [Google Scholar]
  137. YangJ. GaoY. MaoH. KuangX. TianF. Qiju Dihuang Pill protects the lens epithelial cells via alleviating cuproptosis in diabetic cataract.J. Ethnopharmacol.202433311844410.1016/j.jep.2024.118444 38851473
     [Google Scholar]
  138. DascaluA. AnghelacheA. StanaD. CosteaA. NicolaeV. TanasescuD. CosteaD. TribusL. ZguraA. SerbanD. DutaL. TudosieM. BalasescuS. TanasescuC. TudosieM. Serum levels of copper and zinc in diabetic retinopathy: Potential new therapeutic targets (Review).Exp. Ther. Med.202223532410.3892/etm.2022.11253 35386624
     [Google Scholar]
  139. Aloysius DhivyaM. SulochanaK.N. Bharathi DeviS.R. High glucose induced inflammation is inhibited by copper chelation via rescuing mitochondrial fusion protein 2 in retinal pigment epithelial cells.Cell. Signal.20229211024410.1016/j.cellsig.2022.110244 34999205
     [Google Scholar]
  140. DeviS.R.B. Dhivya MA. SulochanaK.N. Copper transporters and chaperones: Their function on angiogenesis and cellular signalling.J. Biosci.201641348749610.1007/s12038‑016‑9629‑6 27581939
     [Google Scholar]
  141. NarayananG. RB.S. VuyyuruH. MuthuvelB. Konerirajapuram NatrajanS. CTR1 silencing inhibits angiogenesis by limiting copper entry into endothelial cells.PLoS One201389e7198210.1371/journal.pone.0071982 24039729
     [Google Scholar]
  142. NarayananI.G. NatarajanS.K. Peptides derived from histidine and methionine‐rich regions of copper transporter 1 exhibit anti‐angiogenic property by chelating extracellular Cu.Chem. Biol. Drug Des.201891379780410.1111/cbdd.13145 29134764
     [Google Scholar]
  143. SmirnovaJ. KabinE. JärvingI. BraginaO. TõuguV. PlitzT. PalumaaP. Copper(I)-binding properties of de-coppering drugs for the treatment of Wilson disease. α-Lipoic acid as a potential anti-copper agent.Sci. Rep.201881146310.1038/s41598‑018‑19873‑2 29362485
     [Google Scholar]
  144. AlaA. AliuE. SchilskyM.L. Prospective pilot study of a single daily dosage of trientine for the treatment of Wilson disease.Dig. Dis. Sci.20156051433143910.1007/s10620‑014‑3495‑6 25605552
     [Google Scholar]
  145. SquittiR. RossiniP.M. CassettaE. MoffaF. PasqualettiP. CortesiM. CollocaA. RossiL. Finazzi-AgróA. d-penicillamine reduces serum oxidative stress in Alzheimer’s disease patients.Eur. J. Clin. Invest.2002321515910.1046/j.1365‑2362.2002.00933.x 11851727
     [Google Scholar]
  146. PanQ. KleerC.G. van GolenK.L. IraniJ. BottemaK.M. BiasC. De CarvalhoM. MesriE.A. RobinsD.M. DickR.D. BrewerG.J. MerajverS.D. Copper deficiency induced by tetrathiomolybdate suppresses tumor growth and angiogenesis.Cancer Res.2002621748544859 12208730
     [Google Scholar]
  147. BradyD.C. CroweM.S. GreenbergD.N. CounterC.M. Copper chelation inhibits BRAFV600E-Driven melanomagenesis and counters resistance to BRAFV600E and MEK1/2 inhibitors.Cancer Res.201777226240625210.1158/0008‑5472.CAN‑16‑1190 28986383
     [Google Scholar]
  148. SammonsS. BradyD. VahdatL. SalamaA.K.S. Copper suppression as cancer therapy: The rationale for copper chelating agents in BRAFV600 mutated melanoma.Melanoma Manag.20163320721610.2217/mmt‑2015‑0005 30190890
     [Google Scholar]
  149. XuM. CasioM. RangeD.E. SosaJ.A. CounterC.M. Copper chelation as targeted therapy in a mouse model of oncogenic braf-driven papillary thyroid cancer.Clin. Cancer Res.201824174271428110.1158/1078‑0432.CCR‑17‑3705 30065097
     [Google Scholar]
  150. BaldariS. Di RoccoG. HeffernM.C. SuT.A. ChangC.J. ToiettaG. effects of copper chelation on BRAFv600e positive colon carcinoma cells.Cancers (Basel)201911565910.3390/cancers11050659 31083627
     [Google Scholar]
  151. CoxC. MerajverS.D. YooS. DickR.D. BrewerG.J. LeeJ.S.J. TeknosT.N. Inhibition of the growth of squamous cell carcinoma by tetrathiomolybdate-induced copper suppression in a murine model.Arch. Otolaryngol. Head Neck Surg.2003129778178510.1001/archotol.129.7.781 12874082
     [Google Scholar]
  152. JuarezJ.C. BetancourtO.Jr Pirie-ShepherdS.R. GuanX. PriceM.L. ShawD.E. MazarA.P. DoñateF. Copper binding by tetrathiomolybdate attenuates angiogenesis and tumor cell proliferation through the inhibition of superoxide dismutase 1.Clin. Cancer Res.200612164974498210.1158/1078‑0432.CCR‑06‑0171 16914587
     [Google Scholar]
  153. KhanM.K. MamouF. SchipperM.J. MayK.S. KwitnyA. WarnatA. BoltonB. NairB.M. KariapperM.S.T. MillerM. BrewerG. NormolleD. MerajverS.D. TeknosT.N. Combination tetrathiomolybdate and radiation therapy in a mouse model of head and neck squamous cell carcinoma.Arch. Otolaryngol. Head Neck Surg.2006132333333810.1001/archotol.132.3.333 16549755
     [Google Scholar]
  154. AghamiriS. JafarpourA. ShojaM. Retracted: Effects of silver nanoparticles coated with anti‐HER2 on irradiation efficiency of SKBR3 breast cancer cells.IET Nanobiotechnol.201913880881510.1049/iet‑nbt.2018.5258 31625520
     [Google Scholar]
  155. KimK.K. HanA. YanoN. RibeiroJ.R. LokichE. SinghR.K. MooreR.G. Tetrathiomolybdate mediates cisplatin-induced p38 signaling and EGFR degradation and enhances response to cisplatin therapy in gynecologic cancers.Sci. Rep.2015511591110.1038/srep15911 26568478
     [Google Scholar]
  156. YooJ.Y. YuJ.G. KakaA. PanQ. KumarP. KumarB. ZhangJ. MazarA. TeknosT.N. KaurB. OldM.O. ATN-224 enhances antitumor efficacy of oncolytic herpes virus against both local and metastatic head and neck squamous cell carcinoma.Mol. Ther. Oncolytics201521500810.1038/mto.2015.8 27119105
     [Google Scholar]
  157. MorisawaA. OkuiT. ShimoT. IbaragiS. OkushaY. OnoM. NguyenT.T. HassanN.M. SasakiA. Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma.Int. J. Oncol.201852398999910.3892/ijo.2018.4242 29328370
     [Google Scholar]
  158. Calderon-AparicioA. CornejoA. OrueA. RieberM. Anticancer response to disulfiram may be enhanced by co-treatment with MEK inhibitor or oxaliplatin: modulation by tetrathiomolybdate, KRAS/BRAF mutations and c-MYC/p53 status.Ecancermedicalscience20191389010.3332/ecancer.2019.890 30792807
     [Google Scholar]
  159. YoshiiJ. YoshijiH. KuriyamaS. IkenakaY. NoguchiR. OkudaH. TsujinoueH. NakataniT. KishidaH. NakaeD. GomezD.E. De LorenzoM.S. TejeraA.M. FukuiH. The copper-chelating agent, trientine, suppresses tumor development and angiogenesis in the murine hepatocellular carcinoma cells.Int. J. Cancer200194676877310.1002/ijc.1537 11745476
     [Google Scholar]
  160. BremS.S. ZagzagD. TsanaclisA.M. GatelyS. ElkoubyM.P. BrienS.E. Inhibition of angiogenesis and tumor growth in the brain. Suppression of endothelial cell turnover by penicillamine and the depletion of copper, an angiogenic cofactor.Am. J. Pathol.1990137511211142 1700617
     [Google Scholar]
  161. CroweA. JackamanC. BeddoesK.M. RicciardoB. NelsonD.J. Rapid copper acquisition by developing murine mesothelioma: Decreasing bioavailable copper slows tumor growth, normalizes vessels and promotes T cell infiltration.PLoS One201388e7368410.1371/journal.pone.0073684 24013775
     [Google Scholar]
  162. YuZ. ZhouR. ZhaoY. PanY. LiangH. ZhangJ.S. TaiS. JinL. TengC.B. Blockage of SLC31A1‐Dependent copper absorption increases pancreatic cancer cell autophagy to resist cell death.Cell Prolif.2019522e1256810.1111/cpr.12568 30706544
     [Google Scholar]
  163. BrewerG.J. DickR.D. GroverD.K. LeClaireV. TsengM. WichaM. PientaK. RedmanB.G. JahanT. SondakV.K. StrawdermanM. LeCarpentierG. MerajverS.D. Treatment of metastatic cancer with tetrathiomolybdate, an anticopper, antiangiogenic agent: Phase I study.Clin. Cancer Res.200061110 10656425
     [Google Scholar]
  164. RedmanB.G. EsperP. PanQ. DunnR.L. HussainH.K. ChenevertT. BrewerG.J. MerajverS.D. Phase II trial of tetrathiomolybdate in patients with advanced kidney cancer.Clin. Cancer Res.20039516661672 12738719
     [Google Scholar]
  165. JainS. CohenJ. WardM.M. KornhauserN. ChuangE. CiglerT. MooreA. DonovanD. LamC. CobhamM.V. SchneiderS. Hurtado RúaS.M. BenkertS. Mathijsen GreenwoodC. ZelkowitzR. WarrenJ.D. LaneM.E. MittalV. RafiiS. VahdatL.T. Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse.Ann. Oncol.20132461491149810.1093/annonc/mds654 23406736
     [Google Scholar]
  166. HenryN.L. DunnR. MerjaverS. PanQ. PientaK.J. BrewerG. SmithD.C. Phase II trial of copper depletion with tetrathiomolybdate as an antiangiogenesis strategy in patients with hormone-refractory prostate cancer.Oncology2006713-416817510.1159/000106066 17641535
     [Google Scholar]
  167. PassH.I. BrewerG.J. DickR. CarboneM. MerajverS. A phase II trial of tetrathiomolybdate after surgery for malignant mesothelioma: final results.Ann. Thorac. Surg.200886238339010.1016/j.athoracsur.2008.03.016 18640301
     [Google Scholar]
  168. SchneiderB.J. LeeJ.S.J. HaymanJ.A. ChangA.C. OrringerM.B. PickensA. PanC.C. MerajverS.D. UrbaS.G. Pre-operative chemoradiation followed by post-operative adjuvant therapy with tetrathiomolybdate, a novel copper chelator, for patients with resectable esophageal cancer.Invest. New Drugs201331243544210.1007/s10637‑012‑9864‑0 22847786
     [Google Scholar]
  169. GartnerE.M. GriffithK.A. PanQ. BrewerG.J. HenjaG.F. MerajverS.D. ZalupskiM.M. A pilot trial of the anti-angiogenic copper lowering agent tetrathiomolybdate in combination with irinotecan, 5-flurouracil, and leucovorin for metastatic colorectal cancer.Invest. New Drugs200927215916510.1007/s10637‑008‑9165‑9 18712502
     [Google Scholar]
  170. FuS. NaingA. FuC. KuoM.T. KurzrockR. Overcoming platinum resistance through the use of a copper-lowering agent.Mol. Cancer Ther.20121161221122510.1158/1535‑7163.MCT‑11‑0864 22491798
     [Google Scholar]
  171. FuS. HouM.M. WhelerJ. HongD. NaingA. TsimberidouA. JankuF. ZinnerR. Piha-PaulS. FalchookG. KuoM.T. KurzrockR. Exploratory study of carboplatin plus the copper-lowering agent trientine in patients with advanced malignancies.Invest. New Drugs201432346547210.1007/s10637‑013‑0051‑8 24306314
     [Google Scholar]
  172. HuangY.F. KuoM.T. LiuY.S. ChengY.M. WuP.Y. ChouC.Y. A dose escalation study of trientine plus carboplatin and pegylated liposomal doxorubicin in women with a first relapse of epithelial ovarian, tubal, and peritoneal cancer within 12 months after platinum-based chemotherapy.Front. Oncol.2019943710.3389/fonc.2019.00437 31179244
     [Google Scholar]
  173. BremS. GrossmanS.A. CarsonK.A. NewP. PhuphanichS. AlaviJ.B. MikkelsenT. FisherJ.D. Phase 2 trial of copper depletion and penicillamine as antiangiogenesis therapy of glioblastoma.Neuro-oncol.20057324625310.1215/S1152851704000869 16053699
     [Google Scholar]
  174. LowndesS.A. AdamsA. TimmsA. FisherN. SmytheJ. WattS.M. JoelS. DonateF. HaywardC. ReichS. MiddletonM. MazarA. HarrisA.L. Phase I study of copper-binding agent ATN-224 in patients with advanced solid tumors.Clin. Cancer Res.200814227526753410.1158/1078‑0432.CCR‑08‑0315 19010871
     [Google Scholar]
  175. LinJ. ZahurakM. BeerT.M. RyanC.J. WildingG. MathewP. MorrisM. CallahanJ.A. GordonG. ReichS.D. CarducciM.A. AntonarakisE.S. A non-comparative randomized phase II study of 2 doses of ATN-224, a copper/zinc superoxide dismutase inhibitor, in patients with biochemically recurrent hormone-naïve prostate cancer.Urol. Oncol.201331558158810.1016/j.urolonc.2011.04.009 21816640
     [Google Scholar]
  176. Excelsior. A Retrospective Study to Assess the Clinical Efficacy and Safety of Trientine in Wilson's Disease Patients.NCT03299829, 2020.
     [Google Scholar]
  177. Safety Study of Tetrathiomolybdate in Patients With Idiopathic Pulmonary Fibrosis.NCT00189176.
     [Google Scholar]
  178. University of British Columbia. Trientine Hydrochloride for the Prevention of Macular Edema After Cataract Surgery in Patients With Type 2 Diabetes MellitusNCT01295073, 2018.
     [Google Scholar]
  179. University of British ColumbiaTrientine Hydrochloride for the Prevention of Macular Edema Associated with Pan-retinal Photocoagulation for Severe Non-proliferative and Proliferative Diabetic Retinopathy.NCT01213888, 2013.
     [Google Scholar]
  180. Duke UniversityA Pilot Study of Trientine with Vemurafenib for the Treatment BRAF Mutated Metastatic Melanoma.NCT02068079, 2015.
     [Google Scholar]
/content/journals/mrmc/10.2174/0113895575308206240911104945
Loading
Copper Dyshomeostasis and Diabetic Complications: Chelation Strategies for Management
Mini Rev Med Chem 25, 277 (2025); https://doi.org/10.2174/0113895575308206240911104945
/content/journals/mrmc/10.2174/0113895575308206240911104945
/content/journals/mrmc/10.2174/0113895575308206240911104945
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): cell death pathways; cell signaling; chelatin; copper metabolism; Cuproptosis; diabetes

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test