New Chemotherapeutic Strategies against Mesenchymal Triple-Negative Breast Cancer: A Deeper Look at the Molecular Level

Chemotherapy regimens that include taxanes and anthracyclines are the main standard treatment approach for triple-negative breast cancer. On the other hand, platinum-based agents have exhibited efficacy in neoadjuvant and metastatic settings. In this study, cell viability was evaluated in the presence of combined administration in mesenchymal triple-negative breast cancer cells, both sensitive (MDA-MB-231) and resistant (MDA-MB-231/R) to cisplatin, as well as in healthy breast cells (MCF-12A). The drug combinations tested were based on a clinically established regimen for breast cancer comprising an anthracycline (doxorubicin), an alkylating agent (cyclophosphamide) and taxanes (docetaxel and paclitaxel). The alkylating agent was replaced with mono and polynuclear complexes of platinum and palladium containing biogenic polyamines – cisplatin, Pd 3 Spd 2 Cl 6 and [Pt 2 Put 2 (NH 3 ) 4 ] 4+ . Fourier transform infrared microspectroscopy was used to assess the cellular response to the drug combinations at the molecular level. Principal component analysis (PCA) was applied to the vibrational data, revealing major metabolic changes associated with DNA, lipids and proteins, which represent the biomarkers of drug-to-cell impact. The main changes were observed in the B-DNA native conformation, as well as in proteins (ν(C=O) from amino acid side chain). These changes may explain the effectiveness of the combined administration with the tested polynuclear compounds.