NMR-based metabolomic analyses of cisplatin resistant SKOV-3 cell line response to [Pt (O,O′-acac)(γ-acac)(DMS)], Ptac2S, treatment: comparison to cisplatin

The novel [Pt (O,O′-acac)(γ-acac)(DMS)], Ptac2S, Pt(II) complex, has recently gained increasing attention as potential anticancer agent for its pharmacological activity shown in different tumour cell lines, studied both in vitro and in vivo. Such studies evidenced that the mechanism of action of Ptac2S, although not completely clarified, involves non-genomic targets. In this study, we describe the application of 1H NMR based metabolomic approaches to evaluate the pharmacological activity of Ptac2S, on the cisplatin resistant Epithelial Ovarian Carcinoma (EOC), SKOV-3 cell line. The metabolic variations of cellular metabolites, in aqueous and lipophilic extracts, and the composition of the corresponding extracellular culture media have been compared to those of cisplatin. Interestingly, based on our results, differently from cisplatin, the Ptac2S is able to act already at 6h after cells treatment, through synergistic effects. These include the decrease of several metabolites involved in membrane modification, Kreb’s cycle and catabolism of carbohydrates and proteins. These results fully confirm the presence of a different mechanism of action of Ptac2S with respect to cisplatin, involving the specific here considered markers.