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Triple-Negative Breast Cancer (TNBC) is the greatest invasive class of breast cancer with a poor prognosis, due to the side-effects exerted by the chemotherapy used and the low effectivity of novel treatments. In this sense, copper compounds have shown to be potentially effective as antitumor agents, attracting increasing interest as alternatives to the usually employed platinum-derived drugs. Therefore, the aim of this work is to identify differentially expressed proteins in MDA-MB-231 cells exposed to two copper(II)-hydrazone complexes using label-free quantitative proteomics and functional bioinformatics strategies to identify the molecular mechanisms through which these copper complexes exert their antitumoral effect in TNBC cells. Both copper complexes increased proteins involved in endoplasmic reticulum stress and unfolded protein response, as well as the downregulation of proteins related to DNA replication and repair. One of the most relevant anticancer mechanisms of action found for CuHL1 and CuHL2 was the down-regulation of gain-of-function-mutant p53. Moreover, we found a novel and interesting effect for a copper metallodrug, which was the down-regulation of proteins related to lipid synthesis and metabolism that could lead to a beneficial decrease in lipid levels.<\/jats:p>","DOI":"10.3390\/ijms24087531","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T03:25:11Z","timestamp":1681961111000},"page":"7531","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Finding New Molecular Targets of Two Copper(II)-Hydrazone Complexes on Triple-Negative Breast Cancer Cells Using Mass-Spectrometry-Based Quantitative Proteomics"],"prefix":"10.3390","volume":"24","author":[{"given":"Lucia M.","family":"Balsa","sequence":"first","affiliation":[{"name":"CEQUINOR (UNLP, CCT-CONICET La Plata, Asociado a CIC), Departamento de Qu\u00edmica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda R.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"CEQUINOR (UNLP, CCT-CONICET La Plata, Asociado a CIC), Departamento de Qu\u00edmica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Ferraresi-Curotto","sequence":"additional","affiliation":[{"name":"Instituto de F\u00edsica La Plata, IFLP (UNLP, CCT-CONICET La Plata), Departamento de F\u00edsica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz S.","family":"Paraj\u00f3n-Costa","sequence":"additional","affiliation":[{"name":"CEQUINOR (UNLP, CCT-CONICET La Plata, Asociado a CIC), Departamento de Qu\u00edmica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0704-2310","authenticated-orcid":false,"given":"Ana C.","family":"Gonzalez-Bar\u00f3","sequence":"additional","affiliation":[{"name":"CEQUINOR (UNLP, CCT-CONICET La Plata, Asociado a CIC), Departamento de Qu\u00edmica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1010-3997","authenticated-orcid":false,"given":"Ignacio E.","family":"Le\u00f3n","sequence":"additional","affiliation":[{"name":"CEQUINOR (UNLP, CCT-CONICET La Plata, Asociado a CIC), Departamento de Qu\u00edmica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata 1900, Argentina"},{"name":"C\u00e1tedra de Fisiopatolog\u00eda, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3322\/caac.21262","article-title":"Global cancer statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.7314\/APJCP.2016.17.2.445","article-title":"Understanding EGFR Signaling in Breast Cancer and Breast Cancer Stem Cells: Overexpression and Therapeutic Implications","volume":"17","author":"Alanazi","year":"2016","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2147\/BCTT.S236483","article-title":"Effect of Clinical and Treatment Factors on Survival Outcomes of Triple Negative Breast Cancer Patients","volume":"12","author":"Wen","year":"2020","journal-title":"Breast Cancer Targets Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"108253","DOI":"10.1016\/j.pharmthera.2022.108253","article-title":"Triple negative breast cancer (TNBC): Non-genetic tumor heterogeneity and immune microenvironment: Emerging treatment options","volume":"237","author":"So","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1007\/s13346-018-0551-3","article-title":"Metastatic and triple-negative breast cancer: Challenges and treatment options","volume":"8","author":"Sapiezynski","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/his.12868","article-title":"Breast cancer stem cells: Are we ready to go from bench to bedside?","volume":"68","author":"Lin","year":"2016","journal-title":"Histopathology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.drudis.2019.02.012","article-title":"Anticancer activity of palladium-based complexes against triple-negative breast cancer","volume":"24","author":"Vojtek","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"606","DOI":"10.2174\/1568009616666160203113957","article-title":"BRCA1-Associated Triple-Negative Breast Cancer and Potential Treatment for Ruthenium-Based Compounds","volume":"16","author":"Hongthong","year":"2016","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nhukeaw, T., Temboot, P., Hansongnern, K., and Ratanaphan, A. (2014). Cellular responses of BRCA1-defective and triple-negative breast cancer cells and in vitro BRCA1 interactions induced by metallo-intercalator ruthenium (II) complexes containing chloro-substituted phenylazopyridine. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-73"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1002\/anie.201510443","article-title":"Breast Cancer Stem Cell Potent Copper (II)-Non-Steroidal Anti-Inflammatory Drug Complexes","volume":"55","author":"Boodram","year":"2016","journal-title":"Angew. Chem.-Int. Ed."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1039\/C5MT00149H","article-title":"Targeting copper in cancer therapy: \u201cCopper That Cancer\u201d","volume":"7","author":"Denoyer","year":"2015","journal-title":"Metallomics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1021\/cr400135x","article-title":"Advances in copper complexes as anticancer agents","volume":"114","author":"Santini","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"510","DOI":"10.2174\/0929867328666211117094550","article-title":"Copper complexes as antitumor agents: In vitro and in vivo evidences","volume":"30","author":"Balsa","year":"2023","journal-title":"Curr. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"112","DOI":"10.2174\/0929867323666160824162546","article-title":"Vanadium, Ruthenium and Copper Compounds: A New Class of Nonplatinum Metallodrugs with Anticancer Activity","volume":"24","author":"Leon","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/anie.201710910","article-title":"A Copper(II) Phenanthroline Metallopeptide That Targets and Disrupts Mitochondrial Function in Breast Cancer Stem Cells","volume":"57","author":"Laws","year":"2018","journal-title":"Angew. Chem.-Int. Ed."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"110975","DOI":"10.1016\/j.jinorgbio.2019.110975","article-title":"Anticancer and antimetastatic activity of copper (II)-tropolone complex against human breast cancer cells, breast multicellular spheroids and mammospheres","volume":"204","author":"Balsa","year":"2019","journal-title":"J. Inorg. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3833","DOI":"10.1039\/C7DT00283A","article-title":"Copper (II) thiosemicarbazone complexes induce marked ROS accumulation and promote nrf2-mediated antioxidant response in highly resistant breast cancer cells","volume":"46","author":"Palamarciuc","year":"2017","journal-title":"Dalt. Trans."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10081","DOI":"10.1002\/chem.201601719","article-title":"Hydroxyl Radical Generation and DNA Nuclease Activity: A Mechanistic Study Based on a Surface-Immobilized Copper Thioether Clip-Phen Derivative","volume":"22","author":"Romo","year":"2016","journal-title":"Chem. A Eur. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11931","DOI":"10.1039\/D1DT01358K","article-title":"Synergy of DNA intercalation and catalytic activity of a copper complex towards improved polymerase inhibition and cancer cell cytotoxicity","volume":"50","author":"Romo","year":"2021","journal-title":"Dalt. Trans."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"716329","DOI":"10.1155\/2008\/716329","article-title":"Proteomic Approaches in Understanding Action Mechanisms of Metal-Based Anticancer Drugs","volume":"2008","author":"Wang","year":"2008","journal-title":"Met. Based Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez, M.R., Balsa, L.M., Piro, O.E., Etcheverr\u00eda, G.A., Garc\u00eda-Tojal, J., Pis-Diez, R., Le\u00f3n, I.E., Paraj\u00f3n-Costa, B.P., and Gonz\u00e1lez-Bar\u00f3, A.C. (2021). Synthesis, crystal structure, spectroscopic characterization, DFT calculations and cytotoxicity assays of a new cu (II) complex with an acylhydrazone Ligand derived from thiophene. Inorganics, 9.","DOI":"10.3390\/inorganics9020009"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e202100520","DOI":"10.1002\/cmdc.202100520","article-title":"Anticancer activity and mechanism of action evaluation of an acylhydrazone Cu (II) complex toward breast cancer cells, spheroids and mammospheres","volume":"17","author":"Balsa","year":"2022","journal-title":"ChemMedChem"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9812","DOI":"10.1039\/D1DT00869B","article-title":"Anticancer activity of a new copper (ii) complex with a hydrazone ligand. Structural and spectroscopic characterization, computational simulations and cell mechanistic studies on 2D and 3D breast cancer cell models","volume":"50","author":"Balsa","year":"2021","journal-title":"Dalt. Trans."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1677\/erc.1.01272","article-title":"Chemotherapy: Induction of stress responses","volume":"13","author":"Tiligada","year":"2006","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"C93","DOI":"10.1152\/ajpcell.00266.2016","article-title":"Endoplasmic reticulum proteostasis: A key checkpoint in cancer","volume":"312","author":"Oakes","year":"2017","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1126\/science.1209038","article-title":"The unfolded protein response: From stress pathway to homeostatic regulation","volume":"334","author":"Walter","year":"2011","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"24306","DOI":"10.1074\/jbc.M109.026583","article-title":"The thioxotriazole copper (II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells","volume":"284","author":"Tardito","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/358015a0","article-title":"P53, Guardian of the Genome","volume":"358","author":"Lane","year":"1992","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/35042675","article-title":"Surfing the p53 network","volume":"408","author":"Vogelstein","year":"2000","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1093\/carcin\/bgs232","article-title":"The rebel angel: Mutant p53 as the driving oncogene in breast cancer","volume":"33","author":"Walerych","year":"2012","journal-title":"Carcinogenesis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7305","DOI":"10.1038\/sj.onc.1209735","article-title":"Mutant p53 in MDA-MB-231 breast cancer cells is stabilized by elevated phospholipase D activity and contributes to survival signals generated by phospholipase D","volume":"25","author":"Hui","year":"2006","journal-title":"Oncogene"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.cell.2009.11.026","article-title":"Mutant p53 Drives Invasion by Promoting Integrin Recycling","volume":"139","author":"Muller","year":"2009","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cell.2009.01.039","article-title":"A Mutant-p53\/Smad Complex Opposes p63 to Empower TGF\u03b2-Induced Metastasis","volume":"137","author":"Adorno","year":"2009","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.ccr.2014.01.021","article-title":"Mutant p53 in cancer: New functions and therapeutic opportunities","volume":"25","author":"Muller","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s13258-013-0154-9","article-title":"Gain-of-function mutant p53-R280K mediates survival of breast cancer cells","volume":"36","author":"Bae","year":"2014","journal-title":"Genes Genom."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/mco2.27","article-title":"Lipid metabolism in cancer progression and therapeutic strategies","volume":"2","author":"Fu","year":"2021","journal-title":"MedComm"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.devcel.2021.04.013","article-title":"Lipid metabolism in cancer: New perspectives and emerging mechanisms","volume":"56","author":"Broadfield","year":"2021","journal-title":"Dev. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s12967-015-0511-3","article-title":"Fatty acid synthase overexpression: Target for therapy and reversal of chemoresistance in ovarian cancer","volume":"13","author":"Bauerschlag","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/nrc.2016.89","article-title":"The multifaceted roles of fatty acid synthesis in cancer","volume":"16","author":"Schulze","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.1158\/1078-0432.CCR-04-1848","article-title":"Cytochrome p450 profile of colorectal cancer: Identification of markers of prognosis","volume":"11","author":"Kumarakulasingham","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"29086","DOI":"10.1074\/jbc.M111.253245","article-title":"Mouse knockout of the cholesterogenic cytochrome p450 lanosterol 14\u03b1-demethylase (Cyp51) resembles antley-bixler syndrome","volume":"286","author":"Keber","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/S0300-9084(00)88884-7","article-title":"Induction of apoptosis in p53-null HL-60 cells by inhibition of lanosterol 14-\u03b1 demethylase","volume":"80","author":"Ferruelo","year":"1998","journal-title":"Biochimie"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"101043","DOI":"10.1016\/j.tranon.2021.101043","article-title":"Influence of cholesterol on cancer progression and therapy","volume":"14","author":"Mayengbam","year":"2021","journal-title":"Transl. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"906670","DOI":"10.3389\/fonc.2022.906670","article-title":"Cholesterol and Its Derivatives: Multifaceted Players in Breast Cancer Progression","volume":"12","author":"Centonze","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/ijc.2910610405","article-title":"Increased LDL receptor mRNA expression in colon cancer is correlated with a rise in plasma cholesterol levels after curative surgery","volume":"61","author":"Niendorf","year":"1995","journal-title":"Int. J. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1159\/000477890","article-title":"Cholesterol Enhances Colorectal Cancer Progression via ROS Elevation and MAPK Signaling Pathway Activation","volume":"42","author":"Wang","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1073\/pnas.1421601112","article-title":"Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma","volume":"112","author":"Guillaumond","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6462","DOI":"10.1038\/onc.2017.247","article-title":"Elevated tumor LDLR expression accelerates LDL cholesterol-mediated breast cancer growth in mouse models of hyperlipidemia","volume":"36","author":"Gallagher","year":"2017","journal-title":"Oncogene"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/nrc2222","article-title":"Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis","volume":"7","author":"Menendez","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Sebastiano, M.R., and Konstantinidou, G. (2019). Targeting long chain acyl-coa synthetases for cancer therapy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153624"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"32576","DOI":"10.18632\/oncotarget.15936","article-title":"NADPH accumulation is responsible for apoptosis in breast cancer cells induced by fatty acid synthase inhibition","volume":"8","author":"Cui","year":"2017","journal-title":"Oncotarget"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.chembiol.2016.04.011","article-title":"Fasnall, a Selective FASN Inhibitor, Shows Potent Anti-tumor Activity in the MMTV-Neu Model of HER2+ Breast Cancer","volume":"23","author":"Alwarawrah","year":"2016","journal-title":"Cell Chem. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.3748\/wjg.v11.i17.2557","article-title":"Involvement of fatty acid-CoA ligase 4 in hepatocellular carcinoma growth: Roles of cyclic AMP and p38 mitogen-activated protein kinase","volume":"11","author":"Liang","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"38719","DOI":"10.18632\/oncotarget.5340","article-title":"A link between lipid metabolism and epithelial-mesenchymal transition provides a target for colon cancer therapy","volume":"6","author":"Vargas","year":"2015","journal-title":"Oncotarget"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.bcp.2018.11.005","article-title":"Acyl-CoA synthetase-4 is implicated in drug resistance in breast cancer cell lines involving the regulation of energy-dependent transporter expression","volume":"159","author":"Orlando","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the origin of cancer cells","volume":"123","author":"Warburg","year":"1956","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.cmet.2020.06.019","article-title":"Mitochondrial Metabolism as a Target for Cancer Therapy","volume":"32","author":"Vasan","year":"2020","journal-title":"Cell Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1158\/0008-5472.CAN-15-2478","article-title":"EGFR Signaling Enhances Aerobic Glycolysis in Triple-Negative Breast Cancer Cells to Promote Tumor Growth and Immune Escape","volume":"76","author":"Lim","year":"2016","journal-title":"Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Lampa, M., Arlt, H., He, T., Ospina, B., Reeves, J., Zhang, B., Murtie, J., Deng, G., Barberis, C., and Hoffmann, D. (2017). Glutaminase is essential for the growth of triple-negative breast cancer cells with a deregulated glutamine metabolism pathway and its suppression synergizes with mTOR inhibition. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0185092"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"E6556","DOI":"10.1073\/pnas.1703791114","article-title":"CDCP1 drives triple-negative breast cancer metastasis through reduction of lipid-droplet abundance and stimulation of fatty acid oxidation","volume":"114","author":"Wright","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1126\/science.abf0529","article-title":"Copper induces cell death by targeting lipoylated TCA cycle proteins","volume":"375","author":"Tsvetkov","year":"2022","journal-title":"Science"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e202213922","DOI":"10.1002\/anie.202213922","article-title":"Photothermally Triggered Copper Payload Release for Cuproptosis-Promoted Cancer Synergistic Therapy","volume":"62","author":"Zhou","year":"2022","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"365","DOI":"10.2174\/1568009054629654","article-title":"The MCM Complex: Its Role in DNA Replication and Implications for Cancer Therapy","volume":"5","author":"Lei","year":"2005","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.cca.2021.02.005","article-title":"The DNA replication regulator MCM6: An emerging cancer biomarker and target","volume":"517","author":"Zeng","year":"2021","journal-title":"Clin. Chim. Acta"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ab.2011.12.041","article-title":"Determination of the drug-DNA binding modes using fluorescence-based assays","volume":"422","author":"Williams","year":"2012","journal-title":"Anal. Biochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"18739","DOI":"10.1074\/jbc.M001217200","article-title":"Identification of a fourth subunit of mammalian DNA polymerase delta","volume":"275","author":"Liu","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/jcb.24968","article-title":"Cancer specificity of promoters of the genes controlling cell proliferation","volume":"116","author":"Kashkin","year":"2015","journal-title":"J. Cell. Biochem."},{"key":"ref_68","first-page":"1351","article-title":"p53 inhibits the expression of p125 and the methylation of POLD1 gene promoter by downregulating the Sp1-induced DNMT1 activities in breast cancer","volume":"9","author":"Zhang","year":"2016","journal-title":"OncoTargets Ther."},{"key":"ref_69","first-page":"5591","article-title":"Elevated expression of POLD1 is associated with poor prognosis in breast cancer","volume":"16","author":"Qin","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"569295","DOI":"10.3389\/fonc.2021.569295","article-title":"Resveratrol Mediates the Apoptosis of Triple Negative Breast Cancer Cells by Reducing POLD1 Expression","volume":"11","author":"Liang","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.3389\/fphar.2022.720076","article-title":"Role of Nrf2 Signaling Cascade in Breast Cancer: Strategies and Treatment","volume":"13","author":"Kumar","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fonc.2017.00078","article-title":"Endoplasmic reticulum stress, unfolded protein response, and cancer cell fate","volume":"7","author":"Corazzari","year":"2017","journal-title":"Front. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Asadzadeh, Z., Safarzadeh, E., Safaei, S., Baradaran, A., Mohammadi, A., Hajiasgharzadeh, K., Derakhshani, A., Argentiero, A., Silvestris, N., and Baradaran, B. (2020). Current approaches for combination therapy of cancer: The role of immunogenic cell death. Cancers, 12.","DOI":"10.20944\/preprints202003.0228.v1"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nrc3380","article-title":"Immunogenic cell death and DAMPs in cancer therapy","volume":"12","author":"Krysko","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1002\/cbic.202000553","article-title":"Immunogenic Cell Death of Breast Cancer Stem Cells Induced by an Endoplasmic Reticulum-Targeting Copper (II) Complex","volume":"21","author":"Kaur","year":"2020","journal-title":"ChemBioChem"},{"key":"ref_76","first-page":"576384","article-title":"Angiogenesis and Breast Cancer","volume":"2010","author":"Schmitt","year":"2010","journal-title":"J. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"485","DOI":"10.3389\/fphar.2022.838133","article-title":"Targeting Angiogenesis in Breast Cancer: Current Evidence and Future Perspectives of Novel Anti-Angiogenic Approaches","volume":"13","author":"Ayoub","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1517\/14728222.2013.840293","article-title":"Targeting ribonucleotide reductase for cancer therapy","volume":"17","author":"Shao","year":"2013","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_79","first-page":"3349","article-title":"RRM2 elicits the metastatic potential of breast cancer cells by regulating cell invasion, migration and VEGF expression via the PI3K\/AKT signaling","volume":"19","author":"Zhuang","year":"2020","journal-title":"Oncol. Lett."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/7531\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:19:07Z","timestamp":1760123947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/7531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,19]]},"references-count":79,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24087531"],"URL":"https:\/\/doi.org\/10.3390\/ijms24087531","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,19]]}}}