Copper in tumors and the use of copper-based compounds in cancer treatment

Journal of Inorganic Biochemistry - Tập 226 - Trang 111634 - 2022
Daniela Almeida da Silva1, Anastasia De Luca2, Rosanna Squitti3, Mauro Rongioletti4, Luisa Rossi5, Camila M.L. Machado6,7, Giselle Cerchiaro1
1Metal Biochemistry and Oxidative Stress Lab, Center for Natural Science and Humanities, Federal University of ABC - UFABC, Avenida dos Estados 5001, Bloco B, Santo André, SP, Brazil
2Fellow of Fondazione Umberto Veronesi, Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy
3Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
4Department of Laboratory Medicine, Research and Development Division, San Giovanni Calibita Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy
5Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy
6Laboratório de Investigação Médica Medicina Nuclear-LIM43, Departamento de Radiologia,Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, Rua Dr Ovídeo Pires de Campos, 872, São Paulo, SP, Brazil
7Centro Translacional em Oncologia-CTO, Departamento de Radiologia e Oncologia, Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, Av. Dr Arnaldo, 451, São Paulo, SP, Brazil

Tài liệu tham khảo

Kim, 2008, Mechanisms for copper acquisition, distribution and regulation, Nat. Chem. Biol., 4, 176, 10.1038/nchembio.72 Ellingsen, 2007, 529 Ding, 2011, The significance of copper chelators in clinical and experimental application, J. Nutr. Biochem., 22, 301, 10.1016/j.jnutbio.2010.06.010 Uauy, 1998 Vulpe, 1999, Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse, Nat. Genet., 21, 195, 10.1038/5979 Waggoner, 1999, The role of copper in neurodegenerative disease, Neurobiol. Dis., 6, 221, 10.1006/nbdi.1999.0250 Klomp, 1997, Identification and functional expression of HAH1, a novel human gene involved in copper homeostasis*, J. Biol. Chem., 272, 9221, 10.1074/jbc.272.14.9221 Wee, 2013, The mammalian copper transporters CTR1 and CTR2 and their roles in development and disease, Int. J. Biochem. Cell Biol., 45, 960, 10.1016/j.biocel.2013.01.018 Puig, 2002, Biochemical and genetic analyses of yeast and human high affinity copper transporters suggest a conserved mechanism for copper uptake*, J. Biol. Chem., 277, 26021, 10.1074/jbc.M202547200 Banci, 2008, Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer, Proc. Natl. Acad. Sci., 105, 6803, 10.1073/pnas.0800019105 Takahashi, 2002 Glerum, 1996, Characterization of COX17, a yeast gene involved in copper metabolism and assembly of cytochrome oxidase*, J. Biol. Chem., 271, 14504, 10.1074/jbc.271.24.14504 Shanbhag, 2019, ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis, Proc. Natl. Acad. Sci. U. S. A., 116, 6836, 10.1073/pnas.1817473116 Bull, 1993, The Wilson disease gene is a putative copper transporting P–type ATPase similar to the Menkes gene, Nat. Genet., 5, 327, 10.1038/ng1293-327 Chelly, 1993, Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein, Nat. Genet., 3, 14, 10.1038/ng0193-14 Yamaguchi, 1993, Isolation and characterization of a human liver cDNA as a candidate gene for Wilson disease, Biochem. Biophys. Res. Commun., 197, 271, 10.1006/bbrc.1993.2471 Bull, 1994, Wilson disease and Menkes disease: new handles on heavy-metal transport, Trends Genet., 10, 246, 10.1016/0168-9525(94)90172-4 Bhattacharjee, 2017, Cellular copper homeostasis: Current concepts on its interplay with glutathione homeostasis and its implication in physiology and human diseases, Metallomics, 9, 1376, 10.1039/C7MT00066A Halliwell, 1984 Ma, 1999, Cupric nitrilotriacetate-induced apoptosis in HL-60 cells: Association with lipid peroxidation, release of cytochrome C from mitochondria, and activation of caspase-3, Free Radical Biol. Med., 27, 227, 10.1016/S0891-5849(99)00083-0 Lombardo, 2003, Prolonged copper depletion induces expression of antioxidants and triggers apoptosis in SH-SY5Y neuroblastoma cells, Cell. Mol. Life Sci., 60, 1733, 10.1007/s00018-003-3153-1 Tsang, 2014, Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance, Nat. Commun., 5, 3446, 10.1038/ncomms4446 Kelner, 2000, The copper transport protein Atox1 promotes neuronal survival*, J. Biol. Chem., 275, 580, 10.1074/jbc.275.1.580 Muller, 2009, ATOX1: a novel copper-responsive transcription factor in mammals?, Int. J. Biochem. Cell Biol., 41, 1233, 10.1016/j.biocel.2008.08.001 Itoh, 2008, Novel role of antioxidant-1 (Atox1) as a copper-dependent transcription factor involved in cell proliferation, J. Biol. Chem., 283, 9157, 10.1074/jbc.M709463200 Kahra, 2015, Human copper chaperone Atox1 translocates to the nucleus but does not bind DNA in vitro, Protein Pept. Lett., 22, 532, 10.2174/0929866522666150506094546 Jung, 2021, Design of artificial metalloenzymes with multiple inorganic elements: the more the merrier, J. Inorg. Biochem., 223, 111552, 10.1016/j.jinorgbio.2021.111552 Solomon, 2006, Spectroscopic methods in bioinorganic chemistry: blue to green to red copper sites, Inorg. Chem., 45, 8012, 10.1021/ic060450d De Vizcaya-Ruiz, 2000, Induction of apoptosis by a novel copper-based anticancer compound, casiopeina II, in L1210 murine leukaemia and CH1 human ovarian carcinoma cells, Toxicol. in Vitro, 14, 1, 10.1016/S0887-2333(99)00082-X Dovinova, 2002, Main Targets of tetraaza macrocyclic copper complex on L1210 murine leukemia cells, Toxicol. in Vitro, 16, 491, 10.1016/S0887-2333(02)00043-7 Höti, 2004, p53-dependent apoptotic mechanism of a new designer bimetallic compound tri-phenyl tin benzimidazolethiol copper chloride (TPT-CuCl2): in vivo studies in Wistar, J. Pharmacol. Exp. Ther., 311, 22, 10.1124/jpet.104.069104 Seth, 2004, In vitro assessment of copper-induced toxicity in the human hepatoma line, Hep G2, Toxicol. in Vitro, 18, 501, 10.1016/j.tiv.2004.01.006 Dobrova, 2016, Structure–antiproliferative activity studies on l-proline-and homoproline-4-N-pyrrolidine-3-thiosemicarbazone hybrids and their nickel (ii), palladium (ii) and, Dalton Trans., 45, 13427, 10.1039/C6DT02784A Gao, 2016, Synthesis, characterization, DNA interaction, apoptosis and molecular docking of Cu(II) and Mn(II) complexes with endo-norbornene-cis-5,6-dicarboxylic acid, Appl. Organomet. Chem., 31 Lin, 2018, Photocytotoxic copper(II) complexes with schiff-base scaffolds for photodynamic therapy, Chem. Eur. J., 24, 4111, 10.1002/chem.201705640 Mahendiran, 2018, Copper complexes as prospective anticancer agents: in vitro and in vivo evaluation, selective targeting of cancer cells by DNA damage and S phase arrest, RSC Adv., 8, 16973, 10.1039/C8RA00954F Nunes, 2018, Protective effects of neocuproine copper chelator against oxidative damage in NSC34 cells, Mutat. Res. Genet. Toxicol. Environ. Mutagen., 836, 62, 10.1016/j.mrgentox.2018.06.019 Davies, 2001, Oxidative stress, antioxidant defenses, and damage removal, repair, and replacement systems, IUBMB Life, 50, 279, 10.1080/713803728 Klaunig, 2004, The role of oxidative stress in carcinogenesis, Annu. Rev. Pharmacol. Toxicol., 44, 239, 10.1146/annurev.pharmtox.44.101802.121851 Jabs, 1999, Reactive oxygen intermediates as mediators of programmed cell death in plants and animals, Biochem. Pharmacol., 57, 231, 10.1016/S0006-2952(98)00227-5 Shi, 2004, Oxidative stress and apoptosis in metal ion-induced carcinogenesis, Free Radical Biol. Med., 37, 582, 10.1016/j.freeradbiomed.2004.03.012 Acilan, 2017, Synthesis, biological characterization and evaluation of molecular mechanisms of novel copper complexes as anticancer agents, Biochim. Biophys. Acta Gen. Subj., 1861, 218, 10.1016/j.bbagen.2016.10.014 Siotto, 2018, Copper imbalance in Alzheimer’s disease: overview of the exchangeable copper component in plasma and the intriguing role albumin plays, Coord. Chem. Rev., 371, 86, 10.1016/j.ccr.2018.05.020 Zimbrean, 2014, Psychiatric aspects of Wilson disease: a review, Gen. Hosp. Psychiatry, 36, 53, 10.1016/j.genhosppsych.2013.08.007 Hoogenraad, 2001 Tümer, 2010, Menkes disease, Eur. J. Hum. Genet., 18, 511, 10.1038/ejhg.2009.187 2020, 2020 Alzheimer’s disease facts and figures, Alzheimers Dement., 16, 391, 10.1002/alz.12068 Kepp, 2019, Copper imbalance in Alzheimer’s disease: convergence of the chemistry and the clinic, Coord. Chem. Rev., 397, 168, 10.1016/j.ccr.2019.06.018 Sensi, 2018, Copper and zinc dysregulation in Alzheimer’s disease, Trends Pharmacol. Sci., 39, 1049, 10.1016/j.tips.2018.10.001 Miotto, 2015, Copper binding to the N-terminally acetylated, naturally occurring form of alpha-synuclein induces local helical folding, J. Am. Chem. Soc., 137, 6444, 10.1021/jacs.5b01911 Torre, 2016, Global cancer incidence and mortality rates and trends - an update, Cancer Epidemiol. Biomark. Prev., 25, 16, 10.1158/1055-9965.EPI-15-0578 Jemal, 2010, Global patterns of cancer incidence and mortality rates and trends, Cancer Epidemiol. Biomark. Prev., 19, 1893, 10.1158/1055-9965.EPI-10-0437 Valko, 2004, Role of oxygen radicals in DNA damage and cancer incidence, Mol. Cell. Biochem., 266, 37, 10.1023/B:MCBI.0000049134.69131.89 Kamangar, 2006, Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world, J. Clin. Oncol., 24, 2137, 10.1200/JCO.2005.05.2308 Ferreira, 2004 Zeidler, 2012 Dias, 2012, Macanismos da toxidez de FGF2 em células malignas dependentes de RAS: bloqueio de divisão celular e estresse proteotóxico Cerignoli, 2006, Regulation of MAP kinases by the VHR dual-specific phosphatase-implications for cell growth and differentiation, Cell Cycle, 5, 2210, 10.4161/cc.5.19.3267 Possik, 2012, Inibidores de BRAF na era da terapia-alvo, Melanoma-Boletim Inf. GBM, 56 Shaul, 2007, The MEK/ERK cascade: from signaling specificity to diverse functions, Biochim. Biophys. Acta, 1773, 1213, 10.1016/j.bbamcr.2006.10.005 Mandal, 2015, Stamping out RAF and MEK1/2 to inhibit the ERK1/2 pathway: an emerging treat to anticancer therapy Stamping out RAF and MEK1/2 to inhibit the ERK1/2 pathway: an emerging threat to anticancer therapy, Oncogene, 1 Han, 2017, Structure, signaling and the drug discovery of the Ras oncogene protein, BMB Rep., 50, 355, 10.5483/BMBRep.2017.50.7.062 Kidger, 2018, ERK1/2 inhibitors: new weapons to inhibit the RAS-regulated RAF-MEK1/2-ERK1/2 pathway, Pharmacol. Ther., 187, 45, 10.1016/j.pharmthera.2018.02.007 Galluzzi, 2018, Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018, Cell Death Differ., 25, 486, 10.1038/s41418-017-0012-4 Linkermann, 2014, Necroptosis, N. Engl. J. Med., 370, 455, 10.1056/NEJMra1310050 Grootjans, 2017, Initiation and execution mechanisms of necroptosis: an overview, Cell Death Differ., 24, 1184, 10.1038/cdd.2017.65 Denisenko, 2018, p53-Autophagy-metastasis link, Cancers (Basel), 10, 148, 10.3390/cancers10050148 Mishra, 2018, Programmed cell death, from a cancer perspective: an overview, Mol. Diagn. Ther., 22, 281, 10.1007/s40291-018-0329-9 Klionsky, 2016, Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition), Autophagy, 12, 1, 10.1080/15548627.2015.1100356 Galluzzi, 2008, Necroptosis: a specialized pathway of programmed necrosis, Cell, 135, 1161, 10.1016/j.cell.2008.12.004 Glücksmann, 1951, Cell deaths in normal vertebrate ontogeny, Biol. Rev., 26, 59, 10.1111/j.1469-185X.1951.tb00774.x Rotilio, 2001, Copper-dependent oxidative stress and neurodegeneration, IUBMB Life, 50, 309, 10.1080/713803724 Saunders, 1966, Death in embryonic systems, Science, 154, 604, 10.1126/science.154.3749.604 D’Arcy, 2019, Cell death: a review of the major forms of apoptosis, necrosis and autophagy, Cell Biol. Int., 43, 582, 10.1002/cbin.11137 MacDonald, 2014, Memo is a copper-dependent redox protein with an essential role in migration and metastasis, Sci. Signal., 7, 10.1126/scisignal.2004870 Urso, 2015, Behind the Link between copper and angiogenesis: established mechanisms and an overview on the role of vascular copper transport systems, J. Vasc. Res., 52, 172, 10.1159/000438485 Hengartner, 2000, Hengartner MOThe biochemistry of apoptosis, Nature, 407, 770, 10.1038/35037710 Zeiss, 2003, The apoptosis-necrosis continuum: Insights from genetically altered mice, Vet. Pathol., 40, 481, 10.1354/vp.40-5-481 Yang, 2019, Copper induces oxidative stress and apoptosis through mitochondria-mediated pathway in chicken hepatocytes, Toxicol. in Vitro, 54, 310, 10.1016/j.tiv.2018.10.017 Liu, 2020, Copper induces oxidative stress and apoptosis in the mouse liver, Oxidative Med. Cell. Longev., 2020, 1 Budihardjo, 1999, Biochemical pathways of caspase activation during apoptosis, Annu. Rev. Cell Dev. Biol., 15, 269, 10.1146/annurev.cellbio.15.1.269 Zhao, 2018, The key role of extracellular vesicles in the metastatic process, Biochim. Biophys. Acta - Rev. Cancer, 1869, 64, 10.1016/j.bbcan.2017.11.005 Hsu, 1994, Changes of serum copper and zinc levels in patients with nasopharyngeal carcinoma by radiotherapy, Biol. Trace Elem. Res., 46, 1, 10.1007/BF02790064 Shetty, 1989, 273 Recombinant, 2013, vol. 25, no. 6, 861 Kalpana, 2011, Evaluating the radioprotective effect of hesperidin in the liver of Swiss albino mice, Eur. J. Pharmacol., 658, 206, 10.1016/j.ejphar.2011.02.031 Lin, 2002, Serum Copper/Zinc Superoxide Dismutase (Cu/Zn SOD) and Gastric Cancer Risk: a case control study, Jpn. J. Cancer Res., 93, 1071, 10.1111/j.1349-7006.2002.tb01207.x Fridlender, 2009, Polarization of tumor-associated neutrophil phenotype by TGF-β: ‘N1’ versus ‘N2’ TAN, Cancer Cell, 16, 183, 10.1016/j.ccr.2009.06.017 Djoko, 2015, The role of copper and zinc toxicity in innate immune defense against bacterial pathogens, J. Biol. Chem., 290, 1854, 10.1074/jbc.R115.647099 Festa, 2012, Copper at the front line of the host-pathogen battle, PLoS Pathog., 8, 9, 10.1371/journal.ppat.1002887 White, 2009, A role for the ATP7A copper-transporting ATPase in macrophage bactericidal activity, J. Biol. Chem., 284, 33949, 10.1074/jbc.M109.070201 Hu, 1998, Copper stimulates proliferation of human endothelial cells under culture, J. Cell. Biochem., 69, 326, 10.1002/(SICI)1097-4644(19980601)69:3<326::AID-JCB10>3.0.CO;2-A Soncin, 1997, Interaction of human angiogenin with copper modulates angiogenin binding to endothelial cells, Biochem. Biophys. Res. Commun., 236, 604, 10.1006/bbrc.1997.7018 Sun, 2017, The association between copper transporters and the prognosis of cancer patients undergoing chemotherapy: a meta-analysis of literatures and datasets, Oncotarget, 8, 16036, 10.18632/oncotarget.13917 Khadem-Ansari, 2019, Copper and zinc in stage i multiple myeloma: Relation with ceruloplasmin, lipid peroxidation, and superoxide dismutase activity, Horm. Mol. Biol. Clin. Invest., 37, 1 Gupte, 2009, Elevated copper and oxidative stress in cancer cells as a target for cancer treatment, Cancer Treat. Rev., 35, 32, 10.1016/j.ctrv.2008.07.004 Shanbhag, 2021, Copper metabolism as a unique vulnerability in cancer, Biochim. Biophys. Acta, Mol. Cell Res., 1868, 118893, 10.1016/j.bbamcr.2020.118893 Akhgarjand, 2018, vol. 8, no. 3, 21 Dos Santos, 2015, Copper uptake in mammary epithelial cells activates cyclins and triggers antioxidant response, Oxidative Med. Cell. Longev., 2015, 10.1155/2015/162876 Gulec, 2014, Silencing of the Menkes copper-transporting ATPase (Atp7a) gene increases cyclin D1 protein expression and impairs proliferation of rat intestinal epithelial (IEC-6) cells, J. Trace Elem. Med. Biol., 28, 459, 10.1016/j.jtemb.2014.07.010 Safi, 2014, Copper signaling axis as a target for prostate cancer therapeutics, Cancer Res., 74, 5891, 10.1158/0008-5472.CAN-13-3527 Blockhuys, 2017, Defining the human copper proteome and analysis of its expression variation in cancers, Metallomics, 9, 112, 10.1039/C6MT00202A Yu, 2020, ATPase copper transporter A, negatively regulated by miR-148a-3p, contributes to cisplatin resistance in breast cancer cells, Clin. Transl. Med., 10, 57, 10.1002/ctm2.19 Blockhuys, 2020, Evaluation of copper chaperone ATOX1 as prognostic biomarker in breast cancer, Breast Cancer, 27, 505, 10.1007/s12282-019-01044-4 Turski, 2012, A novel role for copper in ras/mitogen-activated protein kinase signaling, Mol. Cell. Biol., 32, 1284, 10.1128/MCB.05722-11 Tsang, 2020, Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma, Nat. Cell Biol., 22, 412, 10.1038/s41556-020-0481-4 Brady, 2014, Copper is required for oncogenic BRAF signalling and tumorigenesis, Nature, 509, 492, 10.1038/nature13180 Weintraub, 2015, SOD mimetic activity and antiproliferative properties of a novel tetra nuclear copper (II) complex, J. Biol. Inorg. Chem., 20, 1287, 10.1007/s00775-015-1307-x Aubert, 2020, Copper bioavailability is a KRAS-specific vulnerability in colorectal cancer, Nat. Commun., 11, 1, 10.1038/s41467-020-17549-y Mizutani, 2007, Overexpression of XIAP expression in renal cell carcinoma predicts a worse prognosis, Int. J. Oncol., 30, 919 Hussain, 2017, XIAP over-expression is an independent poor prognostic marker in Middle Eastern breast cancer and can be targeted to induce efficient apoptosis, BMC Cancer, 17, 1, 10.1186/s12885-017-3627-4 Mufti, 2006, XIAP is a copper binding protein deregulated in Wilson’s disease and other copper toxicosis disorders, Mol. Cell, 21, 775, 10.1016/j.molcel.2006.01.033 Brady, 2010, Regulation of the Copper Chaperone CCS by XIAP-Mediated Ubiquitination, Mol. Cell. Biol., 30, 1923, 10.1128/MCB.00900-09 Hou, 2017, Solution structure and interaction with copper in vitro and in living cells of the first BIR domain of XIAP, Sci. Rep., 7, 1, 10.1038/s41598-017-16723-5 Liao, 2020, Inflammation mobilizes copper metabolism to promote colon tumorigenesis via an IL-17-STEAP4-XIAP axis, Nat. Commun., 11, 1, 10.1038/s41467-020-14698-y Hodgkinson, 2012, Copper homeostasis at the host-pathogen interface, J. Biol. Chem., 287, 13549, 10.1074/jbc.R111.316406 Li, 2015, Copper depletion inhibits CoCl2 -induced aggressive phenotype of MCF-7 cells via downregulation of HIF-1 and inhibition of Snail/Twist-mediated epithelial-mesenchymal transition, Sci. Rep., 5, 1 Rigiracciolo, 2015, Copper activates HIF-1α/GPER/VEGF signalling in cancer cells, Oncotarget, 6, 34158, 10.18632/oncotarget.5779 Martin, 2005, Copper-dependent activation of hypoxia-inducible factor (HIF)-1: implications for ceruloplasmin regulation, Blood, 105, 4613, 10.1182/blood-2004-10-3980 Feng, 2009, Copper regulation of hypoxia-inducible factor-1 activity, Mol. Pharm., 75, 174, 10.1124/mol.108.051516 Baker, 2013, Lysyl oxidase enzymatic function increases stiffness to drive colorectal cancer progression through FAK, Oncogene, 32, 1863, 10.1038/onc.2012.202 Blockhuys, 2020, Single-cell tracking demonstrates copper chaperone Atox1 to be required for breast cancer cell migration, Proc. Natl. Acad. Sci. U. S. A., 117, 2014, 10.1073/pnas.1910722117 Payne, 2005, Lysyl oxidase regulates breast cancer cell migration and adhesion through a hydrogen peroxide-mediated mechanism, Cancer Res., 65, 11429, 10.1158/0008-5472.CAN-05-1274 El-Haibi, 2012, Critical role for lysyl oxidase in mesenchymal stem cell-driven breast cancer malignancy, Proc. Natl. Acad. Sci. U. S. A., 109, 17460, 10.1073/pnas.1206653109 Marone, 2004, Memo mediates ErbB2-driven cell motility, Nat. Cell Biol., 6, 515, 10.1038/ncb1134 Okkelman, 2014, Nuclear translocation of lysyl oxidase is promoted by interaction with transcription repressor p66β, Cell Tissue Res., 358, 481, 10.1007/s00441-014-1972-z Harris, 2004, A requirement for copper in angiogenesis, Nutr. Rev., 62, 60, 10.1111/j.1753-4887.2004.tb00025.x Yoshiji, 2003, The copper-chelating agent, trientine, attenuates liver enzyme-altered preneoplastic lesions in rats by angiogenesis suppression, Oncol. Rep., 10, 1369 Narayanan, 2013, CTR1 silencing inhibits angiogenesis by limiting copper entry into endothelial cells, PLoS One, 8, 2, 10.1371/journal.pone.0071982 Narayanan, 2018, Peptides derived from histidine and methionine-rich regions of copper transporter 1 exhibit anti-angiogenic property by chelating extracellular Cu, Chem. Biol. Drug Des., 91, 797, 10.1111/cbdd.13145 Gao, 2008, Mechanisms of action of angiogenin, Acta Biochim. Biophys. Sin. Shanghai, 40, 619, 10.1111/j.1745-7270.2008.00442.x Giacomelli, 2015, Copper (II) ions modulate Angiogenin activity in human endothelial cells, Int. J. Biochem. Cell Biol., 60, 185, 10.1016/j.biocel.2015.01.005 Chen, 2015, Copper transport protein antioxidant-1 promotes inflammatory neovascularization via chaperone and transcription factor function, Sci. Rep., 5, 1 Sudhahar, 2020, Caveolin-1 stabilizes ATP7A, a copper transporter for extracellular SOD, in vascular tissue to maintain endothelial function, Am. J. Phys. Cell Phys., 319, C933 Apte, 2009 Kroemer, 2008 D’Onofrio, 2012 Marques, 2017, Generation of Advanced Glycation End-Products (AGEs) by glycoxidation mediated by copper and ROS in a human serum albumin (HSA) model peptide: reaction mechanism and damage in motor neuron cells, Mutat. Res. Genet. Toxicol. Environ. Mutagen., 824, 42, 10.1016/j.mrgentox.2017.10.005 Siddik, 2003, Cisplatin: Mode of cytotoxic action and molecular basis of resistance, Oncogene, 22, 7265, 10.1038/sj.onc.1206933 Katano, 2002, Acquisition of resistance to cisplatin is accompanied by changes in the cellular pharmacology of copper, Cancer Res., 62, 6559 Kuo, 2021, Targeting the copper transport system to improve treatment efficacies of platinum-containing drugs in cancer chemotherapy, Pharmaceuticals, 14, 10.3390/ph14060549 Lin, 2002, The copper transporter CTR1 regulates cisplatin uptake in Saccharomyces cerevisiae, Mol. Pharmacol., 62, 1154, 10.1124/mol.62.5.1154 Ishida, 2002, Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals, Proc. Natl. Acad. Sci. U. S. A., 99, 14298, 10.1073/pnas.162491399 Liang, 2009, Mechanistic comparison of human high-affinity copper transporter 1-mediated transport between copper ion and cisplatin, Mol. Pharmacol., 76, 843, 10.1124/mol.109.056416 Ishida, 2010, Enhancing tumor-specific uptake of the anticancer drug cisplatin with a copper chelator, Cancer Cell, 17, 574, 10.1016/j.ccr.2010.04.011 Lee, 2011, Prognostic value of the copper transporters, CTR1 and CTR2, in patients with ovarian carcinoma receiving platinum-based chemotherapy, Gynecol. Oncol., 122, 361, 10.1016/j.ygyno.2011.04.025 Akerfeldt, 2017, Interactions of cisplatin and the copper transporter CTR1 in human colon cancer cells, J. Biol. Inorg. Chem., 22, 765, 10.1007/s00775-017-1467-y Bompiani, 2016, Copper transporters and chaperones CTR1, CTR2, ATOX1, and CCS as determinants of cisplatin sensitivity, Metallomics, 8, 951, 10.1039/C6MT00076B Holzer, 2004, Cisplatin rapidly down-regulates its own influx transporter hCTR1 in cultured human ovarian carcinoma cells, Clin. Cancer Res., 10, 6744, 10.1158/1078-0432.CCR-04-0748 Holzer, 2006, The internalization and degradation of human copper transporter 1 following cisplatin exposure, Cancer Res., 66, 10944, 10.1158/0008-5472.CAN-06-1710 Nakayama, 2001, Expression and cisplatin sensitivity of copper-transporting P-type adenosine triphosphatase (ATP7B) in human solid carcinoma cell lines, Oncol. Rep., 8, 1285 Safaei, 2005, Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs, Crit. Rev. Oncol. Hematol., 53, 13, 10.1016/j.critrevonc.2004.09.007 Kuo, 2007, The roles of copper transporters in cisplatin resistance, Cancer Metastasis Rev., 26, 71, 10.1007/s10555-007-9045-3 Zhu, 2017, A role for the ATP7A copper transporter in tumorigenesis and cisplatin resistance, J. Cancer, 8, 1952, 10.7150/jca.19029 Nakayama, 2004, Prognostic value of the Cu-transporting ATPase in ovarian carcinoma patients receiving cisplatin-based chemotherapy, Clin. Cancer Res., 10, 2804, 10.1158/1078-0432.CCR-03-0454 Samimi, 2003, Increase in expression of the copper transporter ATP7A during platinum drug-based treatment is associated with poor survival in ovarian cancer patients, Clin. Cancer Res., 9, 5853 Miyashita, 2003, Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a chemoresistance marker in human oral squamous cell carcinoma treated with cisplatin, Oral Oncol., 39, 157, 10.1016/S1368-8375(02)00038-6 Petruzzelli, 2019, Activity and trafficking of copper-transporting ATPases in tumor development and defense against platinum-based drugs, Cells, 8, 10.3390/cells8091080 Hua, 2011, Distorted copper homeostasis with decreased sensitivity to cisplatin upon chaperone Atox1 deletion in Drosophila, BioMetals, 24, 445, 10.1007/s10534-011-9438-1 Safaei, 2009, Effects of the loss of Atox1 on the cellular pharmacology of cisplatin, J. Inorg. Biochem., 103, 333, 10.1016/j.jinorgbio.2008.11.012 Boal, 2009, Crystal structures of cisplatin bound to a human copper chaperone, J. Am. Chem. Soc., 131, 14196, 10.1021/ja906363t Mariniello, 2019, Synthetic lethality screening identifies FDA-approved drugs that overcome ATP7B-mediated tolerance of tumor cells to cisplatin, bioRxiv Ramachandran, 2020, Molecules synthesis, characterization and biological activity of novel Cu(II) complexes of 6-methyl-2-Oxo-1,2-dihydroquinoline-3-carbaldehyde-4n-subs, Molecules, 25, 1868, 10.3390/molecules25081868 Vančo, 2021, Copper(Ii) complexes containing natural flavonoid pomiferin show considerable in vitro cytotoxicity and anti-inflammatory effects, Int. J. Mol. Sci., 22, 10.3390/ijms22147626 Rochford, 2020, Cu(ii) phenanthroline-phenazine complexes dysregulate mitochondrial function and stimulate apoptosis, Metallomics, 12, 65, 10.1039/c9mt00187e Mo, 2018, Mixed-ligand Cu(II) hydrazone complexes designed to enhance anticancer activity, Eur. J. Med. Chem., 156, 368, 10.1016/j.ejmech.2018.07.022 Chen, 2013, Overcoming platinum drug resistance with copper-lowering agents, Anticancer Res., 33, 4157 Lopez, 2019, Copper depletion as a therapeutic strategy in cancer, Met. Ions Life Sci., 19 Baldari, 2020, Current biomedical use of copper chelation therapy, Int. J. Mol. Sci., 21, 1, 10.3390/ijms21031069 Członkowska, 2018, Wilson disease, Nat. Rev. Dis. Prim., 4, 1 Chan, 2017, Influencing the tumor microenvironment: a phase II study of copper depletion using tetrathiomolybdate in patients with breast cancer at high risk for recurrence and in preclinical models of lung metastases, Clin. Cancer Res., 23, 666, 10.1158/1078-0432.CCR-16-1326 Pass, 2008, A phase II trial of tetrathiomolybdate after surgery for malignant mesothelioma: final results, Ann. Thorac. Surg., 86, 383, 10.1016/j.athoracsur.2008.03.016 Henry, 2006, Phase II trial of copper depletion with tetrathiomolybdate as an antiangiogenesis strategy in patients with hormone-refractory prostate cancer, Oncology, 71, 168, 10.1159/000106066 Fu, 2012, Overcoming platinum resistance through the use of a copper-lowering agent, Mol. Cancer Ther., 11, 1221, 10.1158/1535-7163.MCT-11-0864 Fu, 2014, Exploratory study of carboplatin plus the copper-lowering agent trientine in patients with advanced malignancies, Investig. New Drugs, 32, 465, 10.1007/s10637-013-0051-8 Reedijk, 2003, New clues for platinum antitumor chemistry: kinetically controlled metal binding to DNA, Proc. Natl. Acad. USA, 100, 3611, 10.1073/pnas.0737293100 Todd, 2009, Inhibition of transcription by platinum antitumor compounds, Metallomics, 1, 280, 10.1039/b907567d Niegisch, 2017, Urothelial cancer: update on systemic treatment options, Aktuelle Urol, 48, 340 Tixier, 2017, Comparative toxicities of 3 platinum-containing chemotherapy regimens in relapsed/refractory lymphoma patients, Hematol. Oncol., 35, 584, 10.1002/hon.2328 Jagadeesan, 2013, Water-soluble Co(III) complexes of substituted phenanthrolines with cell selective anticancer activity, Inorg. Chem., 52, 12535, 10.1021/ic4016228 Cao, 2017, G-quadruplex DNA targeted metal complexes acting as potential anticancer drugs, Inorg. Chem. Front., 4, 10, 10.1039/C6QI00300A Gabano, 2018, The cisplatin-based Pt (IV)-diclorofibrato multi-action anticancer prodrug exhibits excellent performances also in hypoxic conditions, Dalton Trans., 47, 8268, 10.1039/C7DT04614F Gailer, 2018, Improving the safety of metal-based drugs by tuning their metabolism with chemoprotective agents, J. Inorg. Biochem., 179, 154, 10.1016/j.jinorgbio.2017.11.008 Wong, 1999, Current status of platinum-based antitumor drugs, Chem. Rev., 99, 2451, 10.1021/cr980420v Li, 2012, Sodium selenosulfate at an innocuous dose markedly prevents cisplatin-induced gastrointestinal toxicity, Toxicol. Appl. Pharmacol., 258, 376, 10.1016/j.taap.2011.11.020 Agudo-López, 2017, Mechanistic added value of a trans-Sulfonamide-Platinum-Complex in human melanoma cell lines and synergism with cis-Platin, Mol. Cancer, 16, 10.1186/s12943-017-0618-7 Ramos, 2020, Rhenium (I) polypyridine complexes coordinated to an ethyl-isonicotinate ligand: Luminescence and in vitro anti-cancer studies, Inorg. Chim. Acta, 501, 10.1016/j.ica.2019.119329 Santini, 2014, Advances in copper complexes as anticancer agents, Chem. Rev., 114, 815, 10.1021/cr400135x Bostancıoğlu, 2014, Investigation of the pharmacological profiles of dinuclear metal complexes as novel, potent and selective cytotoxic agents against ras-transformed cells, Enviro. Toxicol. Pharmacol., 37, 897, 10.1016/j.etap.2014.03.003 Barbosa, 2017, Molecules synthesis, characterization and biological activities of biopolymeric schiff bases prepared with chitosan and salicylaldehydes and their Pd(II) and Pt(II) complexes, Molecules, 22, 10.3390/molecules22111987 Singh, 2017, Aminoacid-derivatized Cu (II) complexes: synthesis, DNA interactions and in vitro cytotoxicity, J. Organomet. Chem., 849–850, 157, 10.1016/j.jorganchem.2017.04.017 Sooriyaarachchi, 2016, Tuning the metabolism of the anticancer drug cisplatin with chemoprotective agents to improve its safety and efficacy, Metallomics, 8, 1170, 10.1039/C6MT00183A Guedes, 2020, Heterobimetallic Ru (ii)/Fe (ii) complexes as potent anticancer agents against breast cancer cells, inducing apoptosis through multiple targets, Metallomics, 4, 547, 10.1039/c9mt00272c Mahnken, 1992, Organic-photochemistry. 98. Toward the development of photo cisplatinum reagents-reaction of cis-dichlorobis (1, 10-phenanthroline) rhodium (III) with calf thymus dna, nucleotides, and nucleosides, J. Am. Chem. Soc., 114, 9253, 10.1021/ja00050a002 Butler, 2012, Tryptophan switch for a photoactivated platinum anticancer complex, J. Am. Chem. Soc., 134, 16508, 10.1021/ja3074159 Niyazi, 2012, Crystal structures of ­[Ru(phen)2dppz]2+ Λ with oligonucleotides containing TA/TA and AT/AT steps show two intercalation modes Article Accepted Version, Nat. Chem., 4, 621, 10.1038/nchem.1397 Pierroz, 2012, Molecular and cellular characterization of the biological effects of ruthenium(II) complexes incorporating 2-pyridyl-2-pyrimidine-4-carboxylic acid, J. Am. Chem. Soc., 134, 20376, 10.1021/ja307288s Cao, 2013, Membrane localized iridium(III) complex induces endoplasmic reticulum stress and mitochondria-mediated apoptosis in human cancer cells, J. Med. Chem., 56, 3636, 10.1021/jm4001665 Zhou, 2016, Copper complexes based on chiral Schiff-base ligands: DNA/BSA binding ability, DNA cleavage activity, cytotoxicity and mechanism of apoptosis Stem cells therapy in various disease View project organometallic complexes with PDT ability View project Copper, Artic. Eur. J. Med. Chem., 114, 244, 10.1016/j.ejmech.2016.02.055 Angel, 2017, Copper (II) complexes possessing alkyl-substituted polypyridyl ligands: structural characterization and in vitro antitumor activity, J. Inorg. Biochem., 166, 12, 10.1016/j.jinorgbio.2016.09.012 Deng, 2018, Co (III) complexes based on α-N-heterocyclic thiosemicarbazone ligands: DNA binding, DNA cleavage, and topoisomerase I/II inhibitory activity studies, J. Mol. Struct., 1167, 33, 10.1016/j.molstruc.2018.04.074 Thompson, 2006, Metal complexes in medicinal chemistry: new vistas and challenges in drug design, Dalton Trans., 761, 10.1039/B513476E Hamble, 2007, Developing new metal-based therapeutics: challenges and opportunities, Dalton Trans., 4929, 10.1039/b706075k Boulikas, 2007 Wheate, 2010, The status of platinum anticancer drugs in the clinic and in clinical trials, Dalton Trans., 39, 8113, 10.1039/c0dt00292e Wang, 2006, Copper in medicine: homeostasis, chelation therapy and antitumor drug design, Curr. Med. Chem., 13, 525, 10.2174/092986706776055742 Canovic, 2017, Impact of aromaticity on anticancer activity of polypyridyl ruthenium(II) complexes: synthesis, structure, DNA/protein binding, lipophilicity and anticancer activity Biocrystallographic Studies on HIV-1 Protease and New Inhibitors View project Candida Vie, JBIC J. Biol. Inorg. Chem., 22, 1007, 10.1007/s00775-017-1479-7 Englinger, 2019, Metal drugs and the anticancer immune response, Chem. Rev., 119, 1519, 10.1021/acs.chemrev.8b00396 Easmon, 2001, Synthesis, cytotoxicity, and antitumor activity of copper(II) and iron(II) complexes of 4N-azabicyclo[3.2.2]nonane Thiosemicarbazones derived from acyl diazines, J. Med. Chem., 44, 2164, 10.1021/jm000979z Ferrari, 2002, Synthesis, characterization and biological activity of two new polymeric copper (II) complexes with α-ketoglutaric acid thiosemicarbazone, J. Inorg. Biochem., 89, 36, 10.1016/S0162-0134(01)00371-3 Baldini, 2004, Copper(II) complexes with substituted thiosemicarbazones of α-ketoglutaric acid: Synthesis, X-ray structures, DNA binding studies, and nuclease and biological activity, Inorg. Chem., 43, 7170, 10.1021/ic049883b Sandra, 2014, Anticancer activity of ferrocenylthiosemicarbazones, Anti-Cancer Agents, 14, 459, 10.2174/18715206113136660365 Pahontu, 2016, Synthesis and Characterization of Novel Cu(II), Pd(II) and Pt(II) Complexes with 8-Ethyl-2-hydroxytricyclo(7.3.1.0 2,7)tridecan-13-one-thiosemicarbazone: antimicrobial and in vitro antiproliferative activity, Molecules, 21, 674, 10.3390/molecules21050674 Palanimuthu, 2013, In vitro and in vivo anticancer activity of copper bis(thiosemicarbazone) complexes, J. Med. Chem., 56, 722, 10.1021/jm300938r Marzano, 2009, Copper Complexes as Anticancer, Anti-Cancer Agents in Medicinal Chemistry(Formerly Current Medicinal Chemistry - Anti-Cancer Agents), 9 Carcelli, 2020, In vitro and in vivo anticancer activity of tridentate thiosemicarbazone copper complexes: Unravelling an unexplored pharmacological target, Eur. J. Med. Chem., 194, 112266, 10.1016/j.ejmech.2020.112266 Han, 2014, Synthesis of water soluble copper(II) complexes: crystal structures, DNA binding, oxidative DNA cleavage, and in vitro anticancer studies, Med. Chem. Res., 23, 2347, 10.1007/s00044-013-0824-9 Cerchiaro, 2006, Oxindoles and copper complexes with oxindole-derivatives as potential pharmacological agents, J. Braz. Chem. Soc., 17, 1473, 10.1590/S0103-50532006000800003 Filomeni, 2007, Pro-apoptotic activity of novel isatin-schiff base copper(II) complexes depends on oxidative stress induction and organelle-selective damage*, J. Biol. Chem., 282, 12010, 10.1074/jbc.M610927200 Cerchiaro, 2005, Isatin-Schiff base copper (II) complexes and their influence on cellular viability, J. Inorg. Biochem., 99, 1433, 10.1016/j.jinorgbio.2005.03.013 Singh, 2003, Synthesis, characterization and antitumor studies of N-aroyl-N′-thioaroylhydrazines and their Co(II), Ni(II), Cu(II) and Zn(II) complexes, BioMetals, 16, 471, 10.1023/A:1022571817364 Ye, 2004, Nickel (ii), copper (ii) and zinc (ii) binding properties and cytotoxicity of tripodal, hexadentate tris (ethylenediamine)–analogue chelators, Dalton Trans., 7, 1304, 10.1039/b403476g Ahmad, 2018, Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of efficacy in xenograft models of nasopharyngeal carcinoma, PLoS One, 13, 1, 10.1371/journal.pone.0191295 Huang, 2017, Synthesis and cytotoxic evaluation of steroidal copper (Cu (II)) complexes, Bioinorg. Chem. Appl., 6 Singh, 2020, Anticancer potency of copper(II) complexes of thiosemicarbazones, J. Inorg. Biochem., 210, 111134, 10.1016/j.jinorgbio.2020.111134 Foo, 2018, Copper complex derived from S-benzyldithiocarbazate and 3-acetylcoumarin induced apoptosis in breast cancer cell, BioMetals, 31, 505, 10.1007/s10534-018-0096-4 Vigato, 2004, The challenge of cyclic and acyclic Schiff bases and related derivatives, Coord. Chem. Rev., 248, 1717, 10.1016/j.cct.2003.09.003 Naqi Ahamad, 2020, Anticancer properties, apoptosis and catecholase mimic activities of dinuclear cobalt(II) and copper(II) Schiff base complexes, Bioorg. Chem., 95, 103561, 10.1016/j.bioorg.2019.103561 Zhang, 2020, Two novel chiral tetranucleate copper-based complexes: crystal structures, nanoparticles, and inhibiting angiogenesis and the growth of human breast cancer by regulating the VEGF/VEGFR2 signal pathway in vitro, Dalton Trans., 49, 6043, 10.1039/D0DT00380H Dankhoff, 2019, Copper(ii) complexes with tridentate Schiff base-like ligands: solid state and solution structures and anticancer activity, Dalton Trans., 48, 15220, 10.1039/C9DT02571E Xia, 2019, A new Schiff base coordinated copper(II) compound induces apoptosis and inhibits tumor growth in gastric cancer, Cancer Cell Int., 19, 81, 10.1186/s12935-019-0801-6 Li, 2015, Synthesis, characterization and anticancer activity of two ternary copper(ІІ) Schiff base complexes, Inorg. Chim. Acta, 432, 198, 10.1016/j.ica.2015.04.012 Gou, 2015, Enhancing the copper(II) complexes cytotoxicity to cancer cells through bound to human serum albumin, J. Inorg. Biochem., 144, 47, 10.1016/j.jinorgbio.2014.12.012 Azzellini, 2001, Diimine-copper (II) complexes promote oxidative damage to biological targets, mediated by glutathione, nitrite, and bicarbonate, J. Inorg. Biochem., 86, 218 Cerchiaro, 2004, Kinetic studies of carbohydrate oxidation catalyzed by novel isatin–Schiff base copper (II) complexes, J. Mol. Catal. A Chem., 221, 29, 10.1016/j.molcata.2004.06.017 Cerchiaro, 2004, Keto-enolic equilibria of an isatin-schiff base copper(II) complex and its reactivity toward carbohydrate oxidation, Transit. Met. Chem., 29, 495, 10.1023/B:TMCH.0000037515.77851.12 Koley Seth, 2016, Structure dependent selective efficacy of pyridine and pyrrole based Cu(II) Schiff base complexes towards in vitro cytotoxicity, apoptosis and DNA-bases binding in ground and excited state, J. Photochem. Photobiol. B Biol., 162, 463, 10.1016/j.jphotobiol.2016.07.012 Kaur, 2020, Immunogenic cell death of breast cancer stem cells induced by an endoplasmic reticulum-targeting copper(II) complex, ChemBioChem, 10.1002/cbic.202000553 Sanz del Olmo, 2020, Copper (II) metallodendrimers combined with pro-apoptotic siRNAs as a promising strategy against breast cancer cells, Pharmaceutics, 12, 727, 10.3390/pharmaceutics12080727 Bao, 2020, A new Schiff base copper(II) complex induces cancer cell growth inhibition and apoptosis by multiple mechanisms, J. Inorg. Biochem., 208, 111103, 10.1016/j.jinorgbio.2020.111103 Eshaghi Malekshah, 2020, Synthesis, characterization, biomedical application, molecular dynamic simulation and molecular docking of schiff base complex of Cu(II) supported on Fe3O4/SiO2/APTS, Int. J. Nanomedicine, 15, 2583, 10.2147/IJN.S231062 Hussain, 2019, Copper(II) complexes as potential anticancer and Nonsteroidal anti-inflammatory agents: In vitro and in vivo studies, Sci. Rep., 9, 5237, 10.1038/s41598-019-41063-x Bulatov, 2018, Isatin-Schiff base-copper (II) complex induces cell death in p53-positive tumors, Cell Death Dis., 4, 103, 10.1038/s41420-018-0120-z Devi, 2015, Synthesis, characterization and antimicrobial activities of mixed ligand transition metal complexes with isatin monohydrazone Schiff base ligands and heterocyclic nitrogen base, Spectrochim. Acta Part A Mol. Biomol. Spectrosc., 135, 710, 10.1016/j.saa.2014.07.041 MacLean, 2019, Copper(II) complexes of coumarin-derived Schiff base ligands: pro- or antioxidant activity in MCF-7 cells?, J. Inorg. Biochem., 197, 110702, 10.1016/j.jinorgbio.2019.110702 Gou, 2017, Design of an anticancer copper(II) prodrug based on the Lys199 residue of the active targeting human serum albumin nanoparticle carrier, Mol. Pharm., 14, 1861, 10.1021/acs.molpharmaceut.6b01074 Lago, 2011, Radical production by hydrogen peroxide/bicarbonate and copper uptake in mammalian cells: Modulation by Cu(II) complexes, J. Inorg. Biochem., 105, 189, 10.1016/j.jinorgbio.2010.10.017 Matias, 2012, Cu(GlyGlyHis) effects on MCF7 cells: copper uptake, reactive oxygen species generation and membrane topography changes, J. Inorg. Biochem., 116, 172, 10.1016/j.jinorgbio.2012.07.012 Ribeiro, 2017, New Cu(II) complexes with pyrazolyl derived Schiff base ligands: Synthesis and biological evaluation, J. Inorg. Biochem., 174, 63, 10.1016/j.jinorgbio.2017.05.011 dos Santos, 2015, Copper uptake in mammary epithelial cells activates cyclins and triggers antioxidant response, Oxidative Med. Cell. Longev., 2015, 1, 10.1155/2015/162876 Parveen, 2020, Enantiomeric copper based anticancer agents promoting sequence-selective cleavage of G-quadruplex telomeric DNA and non-random cleavage of plasmid DNA, Metallomics, 12, 988, 10.1039/d0mt00084a Afsan, 2020, Bioorg. Chem., 94, 103427, 10.1016/j.bioorg.2019.103427 da Silveira, 2008, Double-strand DNA cleavage induced by oxindole-Schiff base copper(II) complexes with potential antitumor activity, J. Inorg. Biochem., 102, 1090, 10.1016/j.jinorgbio.2007.12.033 Parsekar, 2018, DNA binding, cleavage and cytotoxicity studies of three mononuclear Cu(II) chloro-complexes containing N–S donor Schiff base ligands, JBIC J. Biol. Inorg. Chem., 23, 1331, 10.1007/s00775-018-1620-2 Gou, 2017, Structure and biological properties of mixed-ligand Cu(II) Schiff base complexes as potential anticancer agents, Eur. J. Med. Chem., 134, 207, 10.1016/j.ejmech.2017.04.026 Li, 2015, Association of structural modifications with bioactivity in three new copper(II) complexes of Schiff base ligands derived from 5-chlorosalicylaldehyde and amino acids, J. Inorg. Biochem., 146, 52, 10.1016/j.jinorgbio.2015.02.013 Konarikova, 2013, Effect of the Schiff base complex diaqua-(N-salicylidene-l-glutamato) copper(II) monohydrate on human tumor cells, Eur. J. Pharmacol., 721, 178, 10.1016/j.ejphar.2013.09.038 Gouda, 2018, Antitumor activity of pyrrolizines and their Cu(II) complexes: Design, synthesis and cytotoxic screening with potential apoptosis-inducing activity, Eur. J. Med. Chem., 145, 350, 10.1016/j.ejmech.2018.01.009 Demirci, 2017, Poloxamer P85 increases anticancer activity of Schiff base against prostate cancer in vitro and in vivo, Anti-Cancer Drugs, 28, 869, 10.1097/CAD.0000000000000528 Matias, 2013, Diethyldithiocarbamate induces apoptosis in neuroblastoma cells by raising the intracellular copper level, triggering cytochrome c release and caspase activation, Toxicol. in Vitro, 27, 349, 10.1016/j.tiv.2012.08.017 Filomeni, 2011, Biochem. J., 437, 443, 10.1042/BJ20110510 Jiang, 2020, Binuclear Schiff base copper(II) complexes: syntheses, crystal structures, HSA interaction and anti-cancer properties, Inorg. Chim. Acta, 499, 119186, 10.1016/j.ica.2019.119186 Gu, 2019, Mitochondria-localizing N-heterocyclic thiosemicarbazone copper complexes with good cytotoxicity and high antimetastatic activity, Eur. J. Med. Chem., 164, 654, 10.1016/j.ejmech.2019.01.014 Qi, 2018, Piperidylthiosemicarbazones Cu(II) complexes with a high anticancer activity by catalyzing hydrogen peroxide to degrade DNA and promote apoptosis, Eur. J. Med. Chem., 158, 853, 10.1016/j.ejmech.2018.09.034 Wang, 2015, Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation, Nat. Chem., 7, 968, 10.1038/nchem.2381 Jiang, 2017, Pilot Study of 64Cu(I) for PET Imaging of Melanoma, Sci. Rep., 7, 1 Vvere, 2007, Cu-ATSM: A radiopharmaceutical for the PET imaging of hypoxia, Dalton Trans., 43, 4893, 10.1039/b705989b Yoshii, 2011, Internal radiotherapy with copper-64-diacetyl-bis (N4-methylthiosemicarbazone) reduces CD133+ highly tumorigenic cells and metastatic ability of mouse colon carcinoma, Nucl. Med. Biol., 38, 151, 10.1016/j.nucmedbio.2010.08.009 Liu, 2020, Hypoxia imaging and theranostic potential of [64Cu][Cu(ATSM)] and ionic Cu(II) salts: a review of current evidence and discussion of the retention mechanisms, EJNMMI Res., 10, 10.1186/s13550-020-00621-5 Poty, 2018, α-emitters for radiotherapy: from basic radiochemistry to clinical studies—part 1, J. Nucl. Med., 59, 878, 10.2967/jnumed.116.186338 Zhou, 2015, Radio-photothermal therapy mediated by a single compartment nanoplatform depletes tumor initiating cells and reduces lung metastasis in the orthotopic 4T1 breast tumor model, Nanoscale, 7, 19438, 10.1039/C5NR04587H Zhou, 2015, Single agent nanoparticle for radiotherapy and radio-photothermal therapy in anaplastic thyroid cancer, Biomaterials, 57, 41, 10.1016/j.biomaterials.2015.04.013 Li, 2017, Synergistic thermoradiotherapy based on PEGylated Cu3BiS3 ternary semiconductor nanorods with strong absorption in the second near-infrared window, Biomaterials, 112, 164, 10.1016/j.biomaterials.2016.10.024 Meidanchi, 2020, Mg(1-x)Cux Fe2 O4 superparamagnetic nanoparticles as nano-radiosensitizer agents in radiotherapy of MCF-7 human breast cancer cells, Nanotechnology, 31, 325706, 10.1088/1361-6528/ab8cf2 Yi, 2018, Biomimetic copper sulfide for chemo-radiotherapy: enhanced uptake and reduced efflux of nanoparticles for tumor cells under ionizing radiation, Adv. Funct. Mater., 28, 1, 10.1002/adfm.201705161 Yi, 2015, Imaging-guided combined photothermal and radiotherapy to treat subcutaneous and metastatic tumors using iodine-131-doped copper sulfide nanoparticles, Adv. Funct. Mater., 25, 4689, 10.1002/adfm.201502003 Fan, 2019, Poly(amidoamine) dendrimer-coordinated copper(II) complexes as a theranostic nanoplatform for the radiotherapy-enhanced magnetic resonance imaging and chemotherapy of tumors and tumor metastasis, Nano Lett., II Weiss, 2019, Wilson disease summary genetic counseling, GeneReviews®, 1 Martinelli, 2013, MEDNIK syndrome: a novel defect of copper metabolism treatable by zinc acetate therapy, Brain, 136, 872, 10.1093/brain/awt012 Menkes, 1962, A sex-linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration, Pediatrics, 29, 764 Ronce, 1997, A C2055T transition in exon 8 of the ATP7A gene is associated with exon skipping in an occipital horn syndrome family [3], Am. J. Hum. Genet., 61, 233, 10.1016/S0002-9297(07)64297-9 Southon, 2013, Presenilin promotes dietary copper uptake, PLoS One, 8, 2, 10.1371/journal.pone.0062811 Davies, 2016, Copper dyshomoeostasis in Parkinson’s disease: Implications for pathogenesis and indications for novel therapeutics, Clin. Sci., 130, 565, 10.1042/CS20150153 Velugula, 2020, Nuclease and anticancer activity of antioxidant conjugated terpyridine metal complexes, Inorg. Chim. Acta, 507, 119596, 10.1016/j.ica.2020.119596 Ajibade, 2020, Synthesis, characterization and anti-cancer studies of Mn(II), Cu(II), Zn(II) and Pt(II) dithiocarbamate complexes - crystal structures of the Cu(II) and Pt(II) complexes, Inorg. Chim. Acta, 504, 119431, 10.1016/j.ica.2020.119431 Yang, 2019, Copper(ii) complexes with NNO ligands: Synthesis, crystal structures, DNA cleavage, and anticancer activities, Dalton Trans., 48, 17925, 10.1039/C9DT03746B Lu, 2019, Discovery of β-carboline copper(II) complexes as Mcl-1 inhibitor and in vitro and in vivo activity in cancer models, Eur. J. Med. Chem., 181, 10.1016/j.ejmech.2019.111567 Kareem, 2018, Curcumin derived Schiff base ligand and their transition metal complexes: Synthesis, spectral characterization, catalytic potential and biological activity, J. Mol. Struct., 1167, 261, 10.1016/j.molstruc.2018.05.001 Tummalapalli, 2017, Evaluation of DNA/Protein interactions and cytotoxic studies of copper(II) complexes incorporated with N, N donor ligands and terpyridine ligand, Int. J. Biol. Macromol., 95, 1254, 10.1016/j.ijbiomac.2016.11.022 Caruso Bavisotto, 2017, The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex (CubipyOXA) leads to cell death in NCI-H292 cancer cells, J. Inorg. Biochem., 170, 8, 10.1016/j.jinorgbio.2017.02.004 Gou, 2015, Folate-functionalized human serum albumin carrier for anticancer copper(II) complexes derived from natural plumbagin, J. Inorg. Biochem., 153, 13, 10.1016/j.jinorgbio.2015.09.004 Fernandes, 2015, Induction of apoptosis in leukemia cell lines by new copper(II) complexes containing naphthyl groups via interaction with death receptors, J. Inorg. Biochem., 153, 68, 10.1016/j.jinorgbio.2015.09.014 Li, 2014, Synthesis, crystal structure and anticancer activity of a novel ternary copper(II) complex with Schiff base derived from 2-amino-4-fluorobenzoic acid and salicylaldehyde, Inorg. Chem. Commun., 50, 35, 10.1016/j.inoche.2014.10.014 Correia, 2014, Hydroxyquinoline derived vanadium(IV and V) and copper(II) complexes as potential anti-tuberculosis and anti-tumor agents, J. Inorg. Biochem., 141, 83, 10.1016/j.jinorgbio.2014.07.019 Anbu, 2014, Phenyl carbohydrazone conjugated 2-oxoindoline as a new scaffold that augments the DNA and BSA binding affinity and anti-proliferative activity of a 1,10-phenanthroline based copper(II) complex, Inorg. Chim. Acta, 423, 183, 10.1016/j.ica.2014.07.016 Frías González, 2013, Cytotoxic, pro-apoptotic, pro-oxidant, and non-genotoxic activities of a novel copper(II) complex against human cervical cancer, Toxicology, 314, 155, 10.1016/j.tox.2013.08.018 Spoerlein, 2013, Effects of chrysin, apigenin, genistein and their homoleptic copper(II) complexes on the growth and metastatic potential of cancer cells, J. Inorg. Biochem., 127, 107, 10.1016/j.jinorgbio.2013.07.038 Trávníček, 2012, Cellular responses induced by Cu(II) quinolinonato complexes in human tumor and hepatic cells, Chem. Cent. J., 6, 10.1186/1752-153X-6-160 Rajalakshmi, 2012, Copper(II) complexes of terpyridine derivatives: A footstep towards development of antiproliferative agent for breast cancer, J. Inorg. Biochem., 117, 48, 10.1016/j.jinorgbio.2012.08.010 Terenzi, 2012, (Dipyrido[3,2-a:2′,3′-c]phenazine)(glycinato)copper(II) perchlorate: a novel DNA-intercalator with anti-proliferative activity against thyroid cancer cell lines, J. Inorg. Biochem., 117, 103, 10.1016/j.jinorgbio.2012.08.011 Rubner, 2011, Synthesis, characterisation and biological evaluation of copper and silver complexes based on acetylsalicylic acid, Arch. Pharm. (Weinheim)., 344, 684, 10.1002/ardp.201000382 Serment-Guerrero, 2011, Genotoxicity of the copper antineoplastic coordination complexes casiopeinas®, Toxicol. in Vitro, 25, 1376, 10.1016/j.tiv.2011.05.008 Goswami, 2011, Ferrocene-conjugated l-tryptophan copper(II) complexes of phenanthroline bases showing DNA photocleavage activity and cytotoxicity, Inorg. Chem., 50, 8452, 10.1021/ic201028e Roy, 2010, DNA photocleavage and anticancer activity of terpyridine copper(II) complexes having phenanthroline bases, Polyhedron, 29, 2787, 10.1016/j.poly.2010.06.028 Jansson, 2010, Novel thiosemicarbazones of the ApT and DpT series and their copper complexes: Identification of pronounced redox activity and characterization of their antitumor activity, J. Med. Chem., 53, 5759, 10.1021/jm100561b