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 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. Casiopeínas® 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 50–60%, 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.

中文翻译：

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混合螯合铜 (II) 化合物 (Casiopeínas®) 对三阴性乳腺癌体外和体内模型的抗肿瘤和抗转移活性


三阴性乳腺癌 (TNBC) 占所有乳腺癌的 15-20%，是预后和生存率最差的癌症之一。转移是癌症进展的关键过程，导致大多数癌症相关死亡，这凸显了对替代治疗方法的需求。本研究探讨了铜配位化合物 Casiopeína IIIia (CasIIIia) 和 Casiopeína IIgly (CasIIgly) 对 MDA-MB-231 和 4T1 乳腺癌细胞系的体外和体内抗迁移、抗侵袭、抗肿瘤和抗转移作用。体内。这些新兴抗癌剂是混合螯合铜 (II) 化合物，通过产生活性氧 (ROS) 并引起 DNA 损伤来诱导细胞凋亡。通过基因表达阵列进行的全转录组分析表明，亚毒浓度的 CasIIIia 上调参与金属反应机制的基因。 Casiopeínas® 降低 TNBC 细胞活力呈剂量依赖性，且比顺铂更有效。转录组分析证实，在亚毒性浓度 (IC20) 下，它们可抑制 MDA-MB-231 和 4T1 细胞的随机和趋化迁移 50-60%，与顺铂类似。在体内，CasIIIia 和顺铂显着降低了 4T1 细胞同基因乳腺癌模型中的肿瘤生长、体积和重量。此外，与对照组相比，这两种化合物均显着减少了治疗小鼠的转移灶。因此，CasIIIia 和 CasIIgly 是有希望的针对 TNBC 的化疗候选药物。