A NMR‐Based Metabolomic Approach to Investigate the Antitumor Effects of the Novel [Pt(<i>η</i><sup>1</sup>‐C<sub>2</sub>H<sub>4</sub>OMe)(DMSO)(phen)]<sup>+</sup> (phen = 1,10‐Phenanthroline) Compound on Neuroblastoma Cancer Cells
Federica De Castro, Erika Stefàno, Erik De Luca, Antonella Muscella, Santo Marsigliante, Michele Benedetti, Francesco Paolo Fanizzi
Abstract
NMR‐based metabolomics is a very effective tool to assess the tumor response to drugs by providing insights for their mode of action. Recently, a novel Pt(II) complex, [Pt(ƞ 1 ‐C 2 H 4 OMe)(DMSO)(phen)] + (phen = 1,10‐phenanthroline), Pt‐EtOMeSOphen, was synthesized and studied for its antitumor activity against eight human cancer cell lines. Pt‐EtOMeSOphen showed higher cytotoxic effects than cisplatin in most of the cancer cell lines and in particular against the neuroblastoma cell line (SH‐SY5Y). In this study, the mechanism of action of Pt‐EtOMeSOphen on SH‐SY5Y cells was investigated using 1 H NMR‐based metabolomics and compared with cisplatin. The observed time response of SH‐SY5Y cells under treatment revealed a faster action of Pt‐EtOMeSOphen compared with cisplatin, with a response already observed after six hours of exposure, suggesting a cytosolic target. NMR‐based metabolomics demonstrated a peculiar alteration of the glutathione metabolism pathway and the diacylglycerol expression.