{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:44:48Z","timestamp":1792061088299,"version":"4.4.0"},"reference-count":40,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The use of copper nanoparticles (CuNPs) seems to be an alternative therapeutic strategy for cancer therapy due to low-cost synthesis and anticancer activity. In this work, CuNPs\u2019 effects were tested in various concentrations on two types of cells: mesenchymal stem cells (MSCs) and a breast cancer cell line, SKBR3. The concentrations (0.25 mM, 0.5 mM, 1 mM and 2 mM) were first tested on an impedance-based cytotoxicity assay and then used in further cellular metabolic assays. Next, several techniques were applied to test the chosen concentrations: assessment of apoptosis, intracellular reactive oxygen species (ROS) levels, oxidative stress-related gene expression, assessment of mitochondrial respiration and fatty acid methyl ester (FAME) profile evaluation. The higher CuNP concentrations tested on the SKBR3 cell line showed a dose-dependent decrease in the cell index. SKBR3 cells displayed increased CAT and SOD expression, revealed by strong dose-dependent fluorescence. Annexin\/PI staining confirmed increased SKBR3 cell death induced by the higher doses of CuNPs. SKBR3 revealed higher baseline respiratory capacity compared to MSCs. Fatty acid methyl esters (FAMEs) are in higher abundance in MSCs compared to the SKBR3 cell line. The different metabolic response in the tested cells to the CuNPs\u2019 presence could help establish a future personalized treatment for breast cancer patients.<\/jats:p>","DOI":"10.3390\/ijms262110716","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T11:11:16Z","timestamp":1762254676000},"page":"10716","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cellular Metabolic Responses to Copper Nanoparticles: Comparison Between Normal and Breast Cancer Cells"],"prefix":"10.3390","volume":"26","author":[{"given":"Alexandra","family":"Ivan","sequence":"first","affiliation":[{"name":"Department of Functional Sciences, Center of Immuno-Physiology (CIFBIOTEH), University of Medicine and Pharmacy \u201cVictor Babes\u201d, Eftimie Murgu Sq. 2, 300041 Timisoara, Romania"},{"name":"OncoGen Centre, Clinical County Hospital \u201cPius Branzeu\u201d, Blvd. Liviu Rebreanu 156, 300723 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Alexandra","family":"Pricop","sequence":"additional","affiliation":[{"name":"OncoGen Centre, Clinical County Hospital \u201cPius Branzeu\u201d, Blvd. Liviu Rebreanu 156, 300723 Timisoara, Romania"},{"name":"Department of Applied Chemistry and Environmental Engineering and Inorganic Compounds, Faculty of Industrial Chemistry, Biotechnology and Environmental Engineering, Politehnica University Timisoara, Vasile Parvan 6, 300223 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5855-2276","authenticated-orcid":false,"given":"Alexandra Teodora","family":"Lukinich-Gruia","sequence":"additional","affiliation":[{"name":"OncoGen Centre, Clinical County Hospital \u201cPius Branzeu\u201d, Blvd. Liviu Rebreanu 156, 300723 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iustina-Mirabela","family":"Cristea","sequence":"additional","affiliation":[{"name":"OncoGen Centre, Clinical County Hospital \u201cPius Branzeu\u201d, Blvd. Liviu Rebreanu 156, 300723 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7572-3703","authenticated-orcid":false,"given":"Adina","family":"Negrea","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry and Environmental Engineering and Inorganic Compounds, Faculty of Industrial Chemistry, Biotechnology and Environmental Engineering, Politehnica University Timisoara, Vasile Parvan 6, 300223 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioan Bogdan","family":"Pascu","sequence":"additional","affiliation":[{"name":"Research Institute for Renewable Energies-ICER, Politehnica University of Timisoara, 138 Gavril Musicescu Street, 300774 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7304-9716","authenticated-orcid":false,"given":"Crenguta Livia","family":"Calma","sequence":"additional","affiliation":[{"name":"Department of Functional Sciences, Center of Immuno-Physiology (CIFBIOTEH), University of Medicine and Pharmacy \u201cVictor Babes\u201d, Eftimie Murgu Sq. 2, 300041 Timisoara, Romania"},{"name":"OncoGen Centre, Clinical County Hospital \u201cPius Branzeu\u201d, Blvd. Liviu Rebreanu 156, 300723 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"Paunescu","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, Eroii Sanitari Bvd., No. 8, Sector 5, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virgil","family":"Paunescu","sequence":"additional","affiliation":[{"name":"Department of Functional Sciences, Center of Immuno-Physiology (CIFBIOTEH), University of Medicine and Pharmacy \u201cVictor Babes\u201d, Eftimie Murgu Sq. 2, 300041 Timisoara, Romania"},{"name":"OncoGen Centre, Clinical County Hospital \u201cPius Branzeu\u201d, Blvd. Liviu Rebreanu 156, 300723 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3223-0594","authenticated-orcid":false,"given":"Calin Adrian","family":"Tatu","sequence":"additional","affiliation":[{"name":"Department of Functional Sciences, Center of Immuno-Physiology (CIFBIOTEH), University of Medicine and Pharmacy \u201cVictor Babes\u201d, Eftimie Murgu Sq. 2, 300041 Timisoara, Romania"},{"name":"OncoGen Centre, Clinical County Hospital \u201cPius Branzeu\u201d, Blvd. Liviu Rebreanu 156, 300723 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Durgam, L.K., and Oroszi, T.L. (2025). Revolutionizing Healthcare: The Transformative Potential of Nanotechnology in Medicine. Front. Drug Deliv., 5.","DOI":"10.3389\/fddev.2025.1556426"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/s11671-021-03628-6","article-title":"Nanoparticles for Cancer Therapy: Current Progress and Challenges","volume":"16","author":"Gavas","year":"2021","journal-title":"Nanoscale Res. Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1080\/10717544.2022.2039804","article-title":"Metal Nanoparticles as a Promising Technology in Targeted Cancer Treatment","volume":"29","author":"Xu","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.molstruc.2017.09.005","article-title":"Green Synthesis, Morphological and Optical Studies of CuO Nanoparticles","volume":"1150","author":"Reddy","year":"2017","journal-title":"J. Mol. Struct."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"R877","DOI":"10.1016\/j.cub.2011.09.040","article-title":"Copper: An Essential Metal in Biology","volume":"21","author":"Festa","year":"2011","journal-title":"Curr. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ivanova, I.A., Daskalova, D.S., Yordanova, L.P., and Pavlova, E.L. (2024). Copper and Copper Nanoparticles Applications and Their Role against Infections: A Minireview. Processes, 12.","DOI":"10.3390\/pr12020352"},{"key":"ref_7","first-page":"457","article-title":"Cu Nanoparticle: Synthesis, Characterization and Application","volume":"3","author":"Powar","year":"2019","journal-title":"Chem. Methodol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Pricop, A., Negrea, A., Pascu, B., Neme\u015f, N.S., Ciopec, M., Negrea, P., Ian\u0103\u015fi, C., Svera, P., Muntean, D., and Ivan, A. (2025). Copper Nanoparticles Synthesized by Chemical Reduction with Medical Applications. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26041628"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"063011","DOI":"10.1149\/2162-8777\/ac07f8","article-title":"Review\u2014Multifunctional Copper Nanoparticles: Synthesis and Applications","volume":"10","author":"Bhagat","year":"2021","journal-title":"ECS J. Solid. State Sci. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.1039\/D2NA00534D","article-title":"The Toxicity of Nanoparticles and Their Interaction with Cells: An in Vitro Metabolomic Perspective","volume":"5","author":"Awashra","year":"2023","journal-title":"Nanoscale Adv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.2147\/IJN.S130537","article-title":"Cuprous Oxide Nanoparticles Inhibit Prostate Cancer by Attenuating the Stemness of Cancer Cells via Inhibition of the Wnt Signaling Pathway","volume":"12","author":"Wang","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ji, P., Wang, P., Chen, H., Xu, Y., Ge, J., Tian, Z., and Yan, Z. (2023). Potential of Copper and Copper Compounds for Anticancer Applications. Pharmaceuticals, 16.","DOI":"10.3390\/ph16020234"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wo\u017aniak-Budych, M.J., Staszak, K., and Staszak, M. (2023). Copper and Copper-Based Nanoparticles in Medicine\u2014Perspectives and Challenges. Molecules, 28.","DOI":"10.3390\/molecules28186687"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Surya, C., Lakshminarayana, A.B.V., Ramesh, S.H., Kunjiappan, S., Theivendren, P., Santhana Krishna Kumar, A., Ammunje, D.N., and Pavadai, P. (2024). Advancements in Breast Cancer Therapy: The Promise of Copper Nanoparticles. J. Trace Elem. Med. Biol., 86.","DOI":"10.1016\/j.jtemb.2024.127526"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhong, C.-C., Zhao, T., Hogstrand, C., Chen, F., Song, C.-C., and Luo, Z. (2022). Copper (Cu) Induced Changes of Lipid Metabolism through Oxidative Stress-Mediated Autophagy and Nrf2\/PPAR\u03b3 Pathways. J. Nutr. Biochem., 100.","DOI":"10.1016\/j.jnutbio.2021.108883"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101376","DOI":"10.1016\/j.gendis.2024.101376","article-title":"Lipid Metabolism Involved in Progression and Drug Resistance of Breast Cancer","volume":"12","author":"Fu","year":"2025","journal-title":"Genes Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipides from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1002\/smll.201102002","article-title":"How Shape Influences Uptake: Interactions of Anisotropic Polymer Nanoparticles and Human Mesenchymal Stem Cells","volume":"8","author":"Florez","year":"2012","journal-title":"Small"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Merino, J.J., and Caba\u00f1a-Mu\u00f1oz, M.E. (2023). Nanoparticles and Mesenchymal Stem Cell (MSC) Therapy for Cancer Treatment: Focus on Nanocarriers and a Si-RNA CXCR4 Chemokine Blocker as Strategies for Tumor Eradication In Vitro and In Vivo. Micromachines, 14.","DOI":"10.3390\/mi14112068"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12989-017-0209-1","article-title":"Comparison between Micro- and Nanosized Copper Oxide and Water Soluble Copper Chloride: Interrelationship between Intracellular Copper Concentrations, Oxidative Stress and DNA Damage Response in Human Lung Cells","volume":"14","author":"Strauch","year":"2017","journal-title":"Part. Fibre Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"105101","DOI":"10.1088\/1361-6528\/aa57b0","article-title":"Metallic Copper Nanoparticles Induce Apoptosis in a Human Skin Melanoma A-375 Cell Line","volume":"28","author":"Chakraborty","year":"2017","journal-title":"Nanotechnology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3746","DOI":"10.1007\/s12011-022-03458-2","article-title":"Copper Nanoparticles Induce Apoptosis and Oxidative Stress in SW480 Human Colon Cancer Cell Line","volume":"201","author":"Ghasemi","year":"2023","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1007\/s11356-020-09843-5","article-title":"Antitumor Effect of Copper Nanoparticles on Human Breast and Colon Malignancies","volume":"28","author":"Qurtam","year":"2021","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1093\/clinchem\/41.12.1819","article-title":"Lipid Peroxidation and Antioxidants as Biomarkers of Tissue Damage","volume":"41","author":"Gutteridge","year":"1995","journal-title":"Clin. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.chemosphere.2015.09.023","article-title":"Amelioration of Particulate Matter-Induced Oxidative Damage by Vitamin c and Quercetin in Human Bronchial Epithelial Cells","volume":"144","author":"Jin","year":"2016","journal-title":"Chemosphere"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/j.tiv.2009.08.005","article-title":"Copper Oxide Nanoparticles Induce Oxidative Stress and Cytotoxicity in Airway Epithelial Cells","volume":"23","author":"Fahmy","year":"2009","journal-title":"Toxicol. Vitr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1049\/iet-nbt.2017.0140","article-title":"Evaluating the Effect of Green Synthesised Copper Oxide Nanoparticles on Oxidative Stress and Mitochondrial Function Using Murine Model","volume":"12","author":"Ansari","year":"2018","journal-title":"IET Nanobiotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.tiv.2018.10.017","article-title":"Copper Induces Oxidative Stress and Apoptosis through Mitochondria-Mediated Pathway in Chicken Hepatocytes","volume":"54","author":"Yang","year":"2019","journal-title":"Toxicol. In Vitro"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3423","DOI":"10.2147\/IJN.S492145","article-title":"Layered Double Hydroxide Nanoparticles Loaded with Resveratrol Inhibit Glycolysis and Show Efficacy in the Treatment of Breast Cancer","volume":"20","author":"Geng","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"502105","DOI":"10.1155\/2015\/502105","article-title":"Reactive Oxygen Species Are Required for Human Mesenchymal Stem Cells to Initiate Proliferation after the Quiescence Exit","volume":"2015","author":"Lyublinskaya","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"106622","DOI":"10.1016\/j.jddst.2025.106622","article-title":"Advancements in Metal and Metal Oxide Nanoparticles for Targeted Cancer Therapy and Imaging: Mechanisms, Applications, and Safety Concerns","volume":"105","author":"Sidhic","year":"2025","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Tanaka, M., Hsuan, C., Oeki, M., Shen, W., Goda, A., Tahara, Y., Onodera, T., Sanematsu, K., Rikitake, T., and Oki, E. (2020). Identification of Characteristic Compounds of Moderate Volatility in Breast Cancer Cell Lines. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0235442"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Marzec, A., Fotschki, B., Napi\u00f3rkowska, D., Fotschki, J., Cholewi\u0144ska, E., Listos, P., Ju\u015bkiewicz, J., and Ognik, K. (2024). The Effect of Copper Nanoparticles on Liver Metabolism Depends on the Type of Dietary Fiber. Nutrients, 16.","DOI":"10.3390\/nu16213645"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1007\/s00018-019-03092-7","article-title":"Palmitic Acid Is an Intracellular Signaling Molecule Involved in Disease Development","volume":"76","author":"Fatima","year":"2019","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0891-5849(91)90192-6","article-title":"Chemistry and Biochemistry of 4-Hydroxynonenal, Malonaldehyde and Related Aldehydes","volume":"11","author":"Esterbauer","year":"1991","journal-title":"Free Radic. Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bolognesi, A., Chatgilialoglu, A., Polito, L., and Ferreri, C. (2013). Membrane Lipidome Reorganization Correlates with the Fate of Neuroblastoma Cells Supplemented with Fatty Acids. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055537"},{"key":"ref_37","first-page":"3","article-title":"Arachidonic Acid Metabolism: Role in Inflammation","volume":"50","author":"Samuelsson","year":"1991","journal-title":"Z. Rheumatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"106224","DOI":"10.1016\/j.jff.2024.106224","article-title":"Oleic Acid Inhibits the Migration and Invasion of Breast Cancer Cells with Stemness Characteristics through Oxidative Stress-Mediated Attenuation of the FAK\/AKT\/NF-\u03baB Pathway","volume":"116","author":"Kim","year":"2024","journal-title":"J. Funct. Foods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"24364","DOI":"10.18632\/oncotarget.25273","article-title":"Pivotal Role of Human Stearoyl-CoA Desaturases (SCD1 and 5) in Breast Cancer Progression: Oleic Acid-Based Effect of SCD1 on Cell Migration and a Novel pro-Cell Survival Role for SCD5","volume":"9","author":"Angelucci","year":"2018","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pascu, B., Negrea, A., Ciopec, M., Duteanu, N., Negrea, P., Bumm, L.A., Grad (mBuriac), O., Neme\u015f, N.S., Mihalcea, C., and Duda-Seiman, D.M. (2022). Silver Nanoparticle Synthesis via Photochemical Reduction with Sodium Citrate. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010255"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10716\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T05:22:57Z","timestamp":1762406577000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10716"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,4]]},"references-count":40,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262110716"],"URL":"https:\/\/doi.org\/10.3390\/ijms262110716","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,4]]}}}