Triple-Negative Breast Cancer Versus Non-Triple-Negative Breast Cancer: The Impact of Pd and Pt Complexes on...

Breast cancer (BC) is the most common cancer in women, with a high mortality. Triple-negative breast cancer (TNBC) is a biologically aggressive tumour, characterised by high rates of metastasis. Improved chemotherapeutic approaches against BC are therefore an urgent clinical need. In this study, complexes with two and three metal centres linked by the biogenic polyamines: putrescine (Pt₂Put₂(NH₃)₄ and Pd₂Put₂) and spermidine (Pt₃Spd₂ and Pd₃Spd₂), as well as cisplatin were tested against non-malignant (MCF-12A), a TNBC (MDA-MB-468) and a non-TNBC (MCF-7) human cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Fourier transform infrared and Raman microspectroscopies allow to probe biological samples with unmatched sub-cellular spatial resolution. The results revealed that the polynuclear complexes showed activity for the TNBC cell line. While Pd₃Spd₂ showed significant impact on DNA (B-DNA to A- or Z-DNA), Pt₂Put₂(NH₃)₄ had a stronger effect on proteins (seen through Amide II vibrational mode). In addition, these complexes exhibited a greater impact on δC=C-H from phospholipids and CH₂ deformations from lipids. For non-TNBC, Pd₃Spd₂ also displayed a strong contribution from Z-DNA (νOPO_backbone), whereas Pt₂Put₂(NH₃)₄ had a significant impact on Amide I and Amide III signals. This knowledge is expected to contribute for the rational design of improved anticancer drugs, with a higher efficiency coupled to lower toxicity.