Monitoring Apoptotic Activity of Silver(I) Metallodrugs Containing Mefenamic Acid and Mitochondriotropic Agents in Artificial Breast Tumor Tissues

The anticancer potential of silver(I) metallodrugs incorporating mefenamic acid and mitochondriotropic agents in 3D spheroid models of hormone-dependent breast cancer cells (MCF-7) is investigated within this work. The compounds, previously evaluated in 2D cultures, demonstrated potent antiproliferative activity with IC₅₀ values ranging from 1.01 to 5.20 μM, significantly outperforming cisplatin. Here, 3D spheroids are employed to simulate the tumor microenvironment, assessing drug efficacy through morphological changes and apoptosis rates. Compounds 1-4 exhibited dose- and time-dependent reductions in spheroid compactness and sphericity, with compound 2 achieving complete loss of compactness (0%) and sphericity (2%) at 10 μM after 48 h. Apoptotic activity is also significantly higher in 3D spheroids treated with these compounds with respect to their control (25.8%-41.4%), in contrast to cisplatin (24.4%) and untreated cells (8.0%). The results validate the superior efficacy of silver(I) complexes in disrupting tumor integrity and inducing apoptosis. This study underscores the potential of 3D spheroid models for preclinical evaluation and highlights silver(I) metallodrugs as promising candidates for breast cancer therapy. Future research should focus on in vivo validation to further explore their therapeutic applications.