Abstract
Triple-negative breast cancer (TNBC) is the most aggressive type of breast tumor with the worst prognosis. New chemotherapeutic agents against TNBC are essential, aiming at a higher efficacy regarding cell growth inhibition and decreased angiogenesis and invasiveness coupled to lower acquired resistance and deleterious side effects. In this study, Raman and Fourier Transform Infrared (FTIR) microspectroscopies were applied to assess the impact of a trinuclear palladium-spermidine complex on human healthy and mesenchymal TNBC cells, with the results being compared to the clinically used drug cisplatin. To understand the metabolic impact of the drugs at the molecular level and identify the main biomarkers, unsupervised multivariate analysis of the data (Principal Component Analysis and Hierarchical Cluster Analysis) was applied to the vibrational data. The results revealed that the new palladium (Pd) agent had a higher effect on the cellular lipids relative to the platinum (Pt) compound (cisplatin), while the latter showed a stronger impact on the proteins. Besides lipids, Pd-agent showed a higher impact in conformational changes from the B-DNA native conformation to either Z- or A-DNA. This suggests the occurrence of distinct pathways of cytotoxicity for these metal complexes. Also, when comparing cisplatin-sensitive to cisplatin-resistant cells, Pd-agent had a more significant impact on νOPO(backbone) from DNA, δCH(2) from lipids and ν(s)CC(ring) from phenylalanine of cisplatin-sensitive cells, while in cisplatin-resistant cells, proteins were the most affected cell components. These results provided spectral features specific to malignancy that led to discrimination between drug-treated and untreated cells. This knowledge is essential for the rational design of improved drugs with a higher efficiency coupled to lower toxicity.