Antitumoral and Antimetastatic Activity by Mixed Chelate Copper(II) Compounds (Casiopeínas®) on Triple-Negative Breast Cancer - In Vitro and In Vivo Models

Sep 21, 2026

Triple-negative breast cancer (TNBC), responsible for 15–20% of breast cancers, has poor prognosis and survival, with metastasis driving most cancer-related deaths. This study evaluates Casiopeínas® copper coordination compounds CasIIIia and CasIIgly for anti-migratory, anti-invasive, anti-tumoral, and antimetastatic effects in vitro and in vivo. The compounds induce apoptosis via reactive oxygen species and DNA damage and reduce TNBC viability dose-dependently, outperforming Cisplatin. CasIIIia and CasIIgly also suppress migration and inhibit tumor growth and metastatic foci in a syngeneic 4T1 model.

LanguageEnglish

CategoryHealthcare

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Reading Time48 min

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Abstract

Introduction

Article Antitumoral and Antimetastatic Activity by Mixed Chelate Copper(II) Compounds (Casiopeínas® ) on Triple-Negative Breast Cancer, In Vitro and In Vivo Models Mauricio M. González-Ballesteros 1, Luis Sánchez-Sánchez 2, Adrián Espinoza-Guillén 1, Jesús Espinal-Enríquez 3, Carmen Mejía 4, Enrique Hernández-Lemus 3 and Lena Ruiz-Azuara 1, * Citation: González-Ballesteros, M.M.; Sánchez-Sánchez, L.; Espinoza-Guillén, A.; Espinal-Enríquez, J.; Mejía, C.; Hernández-Lemus, E.; Ruiz-Azuara, L. Antitumoral and Antimetastatic Activity by Mixed Chelate Copper(II) Compounds (Casiopeínas®) on Triple-Negative Breast Cancer, In Vitro and In Vivo Models. Int. J. Mol. Sci. 2024, 25, 8803. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms25168803](10.3390/ijms25168803) Academic Editors: Ignacio Camacho-Arroyo, Jorge Melendez-Zajgla, Mauricio Rodriguez-Dorantes and Mahara A. Valverde Ramírez Received: 4 July 2024 Revised: 1 August 2024 Accepted: 3 August 2024 Published: 13 August 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico; [mauricio.gb.117@outlook.com](mauricio.gb.117@outlook.com) (M.M.G.-B.) 2 Laboratorio de Biología Molecular del Cáncer, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México 09230, Mexico 3 Departamento de Genómica Computacional, Instituto Nacional de Medicina Genómica, Ciudad de México 14610, Mexico 4 Laboratorio de Biomedicina Interdisciplinaria, Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Ciudad de México 76230, Mexico * Correspondence: [lenar701@gmail.com](lenar701@gmail.com) Abstract: Triple-negative breast cancer (TNBC), accounting for 15–20% of all breast cancers, has one of the poorest prognoses and survival rates. 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 Casiopeína IIIia (CasIIIia) and Casiopeína IIgly (CasIIgly) on MDAMB-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. Casiopeínas® reduced TNBC cell viability dose-dependently and more efficiently than Cisplatin. At subtoxic concentrations (IC 20), they inhibited random and chemotactic migration of MDA-MB-231 and 4T1 cells by 50–60%, 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. Keywords: triple-negative breast cancer; metastasis; metallodrugs; copper; casiopeína 1. Introduction Cancer is a term that defines a set of multifactorial diseases, where malignant cells possess various phenotypic abnormalities, such as loss of differentiation, a high proliferation rate, and malignant tumors that tend to grow invasively, destroying surrounding as well as distant normal tissues and orga

FAQs

What research question does the study address about TNBC?

The study evaluates whether mixed chelate copper(II) compounds Casiopeínas® (CasIIIia and CasIIgly) can produce antitumoral and antimetastatic effects against triple-negative breast cancer in vitro and in vivo.

How do Casiopeínas® compounds induce cancer cell death according to the study?

They induce apoptosis by generating reactive oxygen species (ROS) and causing DNA damage, as described in the abstract.

How do Casiopeínas® compare with Cisplatin in TNBC experiments?

Casiopeínas® reduce TNBC cell viability dose-dependently and inhibit migration at subtoxic concentrations; in vivo, CasIIIia and Cisplatin reduce tumor growth and metastatic foci, with Casiopeínas® reported as more efficient in cell viability assays.

Sep 21, 2026

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