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Metastasis, a critical process in cancer progression, causes most cancer-related deaths, underscoring the need for alternative therapeutic approaches. This study explores the anti-migratory, anti-invasive, anti-tumoral, and antimetastatic effects of copper coordination compounds Casiope\u00edna IIIia (CasIIIia) and Casiope\u00edna IIgly (CasIIgly) on MDA-MB-231 and 4T1 breast carcinoma cell lines in vitro and in vivo. These emerging anticancer agents, mixed chelate copper(II) compounds, induce apoptosis by generating reactive oxygen species (ROS) and causing DNA damage. Whole-transcriptome analysis via gene expression arrays indicated that subtoxic concentrations of CasIIIia upregulate genes involved in metal response mechanisms. Casiope\u00ednas\u00ae reduced TNBC cell viability dose-dependently and more efficiently than Cisplatin. At subtoxic concentrations (IC20), they inhibited random and chemotactic migration of MDA-MB-231 and 4T1 cells by 50\u201360%, similar to Cisplatin, as confirmed by transcriptome analysis. In vivo, CasIIIia and Cisplatin significantly reduced tumor growth, volume, and weight in a syngeneic breast cancer model with 4T1 cells. Furthermore, both compounds significantly decreased metastatic foci in treated mice compared to controls. Thus, CasIIIia and CasIIgly are promising chemotherapeutic candidates against TNBC.<\/jats:p>","DOI":"10.3390\/ijms25168803","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T05:23:27Z","timestamp":1723613007000},"page":"8803","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Antitumoral and Antimetastatic Activity by Mixed Chelate Copper(II) Compounds (Casiope\u00ednas\u00ae) on Triple-Negative Breast Cancer, In Vitro and In Vivo Models"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4435-1227","authenticated-orcid":false,"given":"Mauricio M.","family":"Gonz\u00e1lez-Ballesteros","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica Inorg\u00e1nica y Nuclear, Facultad de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"S\u00e1nchez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Molecular del C\u00e1ncer, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 09230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adri\u00e1n","family":"Espinoza-Guill\u00e9n","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Inorg\u00e1nica y Nuclear, Facultad de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8707-2511","authenticated-orcid":false,"given":"Jes\u00fas","family":"Espinal-Enr\u00edquez","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00f3mica Computacional, Instituto Nacional de Medicina Gen\u00f3mica, Ciudad de M\u00e9xico 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3210-4213","authenticated-orcid":false,"given":"Carmen","family":"Mej\u00eda","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomedicina Interdisciplinaria, Facultad de Ciencias Naturales, Universidad Aut\u00f3noma de Quer\u00e9taro, Ciudad de M\u00e9xico 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1872-1397","authenticated-orcid":false,"given":"Enrique","family":"Hern\u00e1ndez-Lemus","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00f3mica Computacional, Instituto Nacional de Medicina Gen\u00f3mica, Ciudad de M\u00e9xico 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3035-4507","authenticated-orcid":false,"given":"Lena","family":"Ruiz-Azuara","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Inorg\u00e1nica y Nuclear, Facultad de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,13]]},"reference":[{"key":"ref_1","first-page":"1016","article-title":"Revisiting the hallmarks of cancer","volume":"7","author":"Fouad","year":"2017","journal-title":"Am. 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