Monitoring Apoptotic Activity of Silver(I) Metallodrugs Containing Mefenamic Acid and Mitochondriotropic Agents in
Christina N Banti1, Sotiris K Hadjikakou1,2
1Biological Inorganic Chemistry laboratory, Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece.
Abstract:
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.
Insights
Silver(I) metallodrugs show potent anticancer effects against hormone-dependent breast cancer cells in 3D spheroid models. These novel compounds effectively disrupt tumor integrity and induce apoptosis, outperforming cisplatin in preclinical evaluations.
Area of Science:
- Medicinal Chemistry
- Cancer Biology
- Drug Discovery
Background:
- Silver(I) metallodrugs incorporating mefenamic acid and mitochondriotropic agents were previously effective in 2D cultures.
- These compounds demonstrated significant antiproliferative activity, outperforming cisplatin.
Purpose of the Study:
- To investigate the anticancer potential of silver(I) metallodrugs in 3D spheroid models of hormone-dependent breast cancer cells (MCF-7).
- To evaluate drug efficacy through morphological changes and apoptosis rates within a simulated tumor microenvironment.
Main Methods:
- Utilized 3D spheroid models to mimic the tumor microenvironment.
- Assessed drug efficacy by measuring morphological changes (compactness, sphericity) and apoptosis rates.
- Compared the efficacy of silver(I) complexes (compounds 1-4) against cisplatin and untreated controls.
Main Results:
- Compounds 1-4 reduced spheroid compactness and sphericity in a dose- and time-dependent manner.
- Compound 2 achieved complete loss of compactness (0%) and sphericity (2%) at 10 μM after 48 h.
- Silver(I) complexes significantly increased apoptotic activity (25.8%-41.4%) compared to cisplatin (24.4%) and controls (8.0%).
Conclusions:
- Silver(I) metallodrugs exhibit superior efficacy in disrupting tumor integrity and inducing apoptosis in 3D breast cancer models.
- 3D spheroid models are valuable for preclinical evaluation of anticancer agents.
- Silver(I) complexes represent promising candidates for future breast cancer therapy, warranting further in vivo validation.
