{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:03:34Z","timestamp":1790899414761,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","award":["PIP 2051"],"award-info":[{"award-number":["PIP 2051"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003947","name":"Universidad Nacional de La Plata","doi-asserted-by":"publisher","award":["EX005"],"award-info":[{"award-number":["EX005"]}],"id":[{"id":"10.13039\/501100003947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2024,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>New therapeutic strategies for osteosarcoma (OS) have demonstrated the potential efficacy of copper compounds as anticancer drugs and as a substitute for the often used platinum compounds. OS is a type of bone cancer, primarily affecting young adults and children.The main objective of this work is to discover the molecular targets and cellular pathways related to the antitumor properties of a Cu(II)\u2010hydrazone toward human OS 2D and 3D systems. Cell viability study using MG\u201063 cells was evaluated in OS monolayer and spheroids. CuHL significantly reduced cell viability in OS models (IC<jats:sub>50<\/jats:sub> 2D: 2.6\u00b10.3\u2005\u03bcM; IC<jats:sub>50<\/jats:sub> 3D: 9.9\u00b11.4\u2005\u03bcM) (p&lt;0.001). Also, CuHL inhibits cell proliferation and it induces cells to apoptosis. The main mechanism of action found for CuHL are the interaction with DNA, genotoxicity, the ROS generation and the proteasome activity inhibition. Besides, 67 differentially expressed proteins were found using proteomic approaches. Of those 67 proteins, 40 were found overexpressed and 27 underexpressed. The response to stress and to unfolded protein, as well as ATP synthesis were the most affected biological process among upregulated proteins, whilst proteins related to DNA replication and redox homeostasis were downregulated.<\/jats:p>","DOI":"10.1002\/cbic.202400373","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T15:28:49Z","timestamp":1723217329000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Deciphering the Effect of a Cu(II)\u2010hydrazone Complex on Intracellular Cell Signalling Pathways in a Human Osteosarcoma 2D and 3D Models"],"prefix":"10.1002","volume":"25","author":[{"given":"Luc\u00eda 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  Blvd. 120\u2005N\u00b0 1465 La Plata (1900) Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Santa Maria de la Parra","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  Blvd. 120\u2005N\u00b0 1465 La Plata (1900) Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Ferretti","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  Blvd. 120\u2005N\u00b0 1465 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  Blvd. 120\u2005N\u00b0 1465 La Plata (1900) Argentina"},{"name":"C\u00e1tedra de Fisiopatolog\u00eda Departamento de Ciencias Biol\u00f3gicas Facultad de Ciencias Exactas Universidad Nacional de La Plata  47 y 115 La Plata 1900) Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.77"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-43032-0_1"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737140.2016.1168697"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2017-0317"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389557515666151001142012"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.5b00597"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1691"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867323666160824162546"},{"key":"e_1_2_8_10_1","unstructured":"S. Thota D.\u2005A. Rodrigues D.\u2005C. Crans E.\u2005J. Barreiro J. Med. Chem.2018 acs.jmedchem.7b01689."},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","unstructured":"D. Denoyer S.\u2005A.\u2005S. Clatworthy M.\u2005A. Cater Copper Complexes in Cancer Therapy 2018 18 469-506.","DOI":"10.1515\/9783110470734-016"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24091761"},{"key":"e_1_2_8_13_1","first-page":"1","volume":"17","author":"Balsa L. M.","year":"2021","journal-title":"ChemMedChem."},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2019.110975"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1DT00869B"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7DT01955F"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.inorgchem.9b01195"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2020.111166"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-018-0154-y"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871520616666160513130204"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ica.2018.11.039"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2023.110685"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","unstructured":"P. Levin M.\u2005C. Ruiz A.\u2005I.\u2005B. Romo O.\u2005R. Nascimento A.\u2005L. Di Virgilio A.\u2005G. Oliver A.\u2005P. Ayala I.\u2005C.\u2005N. Diogenes I. Leon L.\u2005A. Lemus Inorg. Chem. Front.2021 8 3238\u20133252.","DOI":"10.1039\/D1QI00233C"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7DT00283A"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7QI00446J"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/inorganics9020009"},{"key":"e_1_2_8_27_1","doi-asserted-by":"crossref","unstructured":"Y. Burgos-L\u00f3pez L.\u2005M. Balsa O.\u2005E. Piro I.\u2005E. Le\u00f3n J. Garc\u00eda-Tojal G.\u2005A. Echeverr\u00eda A.\u2005C. Gonz\u00e1lez-Bar\u00f3 B.\u2005S. Paraj\u00f3n-Costa Polyhedron2022 213 115621.","DOI":"10.1016\/j.poly.2021.115621"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","unstructured":"L. Santa Maria de la Parra A.\u2005I.\u2005B. Romo J. Rodr\u00edguez-L\u00f3pez O.\u2005R. Nascimento G.\u2005A. Echeverr\u00eda O.\u2005E. Piro I.\u2005E. Le\u00f3n Inorg. Chem.2024 63 4925\u20134938.","DOI":"10.1021\/acs.inorgchem.3c04085"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22147626"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1039\/c8mt00369f"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/150845"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0320(19980101)31:1<1::AID-CYTO1>3.0.CO;2-R"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867323666160824162546"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2018.01.008"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4RA09448D"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4DT03764B"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2016.11.024"},{"key":"e_1_2_8_38_1","first-page":"1","volume":"12","author":"Magdy G.","year":"2022","journal-title":"Sci. Reports"},{"key":"e_1_2_8_39_1","doi-asserted-by":"crossref","unstructured":"M.\u2005M. Ramana R. Betkar A. Nimkar P. Ranade B. Mundhe S. Pardeshi J. Photochem. Photobiol. B Biol.2015 151 194\u2013200.","DOI":"10.1016\/j.jphotobiol.2015.08.012"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2011.12.041"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8NJ06274A"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201607216"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867328666211117094550"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.10.696"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.101084"},{"key":"e_1_2_8_46_1","doi-asserted-by":"crossref","unstructured":"Budenholzer C.\u2005L. Cheng Y. Li M. Hochstrasser J. Mol. Biol.2017 22 3500\u20133524.","DOI":"10.1016\/j.jmb.2017.05.027"},{"key":"e_1_2_8_47_1","first-page":"2615","volume":"59","author":"Adams J. J. J.","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr400135x"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.9b00284"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00266.2016"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1209038"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1677\/erc.1.01272"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2020-0157"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgi315"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00001.2015"},{"key":"e_1_2_8_56_1","first-page":"1","volume":"13","author":"Cong F.","year":"2022","journal-title":"Front. Genet."},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2021.02.005"},{"key":"e_1_2_8_58_1","first-page":"1","volume":"8","author":"Zhou J.","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.08.015"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-021-06241-z"},{"key":"e_1_2_8_61_1","doi-asserted-by":"crossref","unstructured":"T. Ismail Y. Kim H. Lee D.\u2005S. Lee H.\u2005S. Lee Int. J. Mol. Sci.2019 20 4407.","DOI":"10.3390\/ijms20184407"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(88)90265-0"}],"container-title":["ChemBioChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.202400373","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:17:42Z","timestamp":1760296662000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cbic.202400373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,24]]},"references-count":62,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2024,11,18]]}},"alternative-id":["10.1002\/cbic.202400373"],"URL":"https:\/\/doi.org\/10.1002\/cbic.202400373","archive":["Portico"],"relation":{},"ISSN":["1439-4227","1439-7633"],"issn-type":[{"value":"1439-4227","type":"print"},{"value":"1439-7633","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,24]]},"assertion":[{"value":"2024-04-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202400373"}}