A NMR‐Based Metabolomic Approach to Investigate the Antitumor Effects of the Novel [Pt(η¹‐C₂H₄OMe)(DMSO)(phen)]⁺ (phen = 1,10‐Phenanthroline) Compound on Neuroblastoma Cancer Cells

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(ƞ1-C2H4OMe)(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 1H 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.

Platinum-Nucleos(t)ide Compounds as Possible Antimetabolites for Antitumor/Antiviral Therapy: Properties and Perspectives

“…When used as adjuvants, they can also improve the effectiveness of antiviral drugs and vaccines [ 61 ]. Anticancer metal-based drugs can act via metal–DNA or metal–protein adducts formation (thus, through a genomic or non-genomic target), then activating specific mechanisms leading to cancer cell death [ 62 , 63 , 64 ].…”

Evaluation of the Antitumor Effects of Platinum-Based [Pt(η1-C2H4-OR)(DMSO)(phen)]+ (R = Me, Et) Cationic Organometallic Complexes on Chemoresistant Pancreatic Cancer Cell Lines

“…We previously synthesized the [Pt(η 1 -C 2 H 4 -OMe) Cl(phen)] precursor leading by direct reaction with DMSO, to the formation of [Pt(η 1 -C 2 H 4 -OMe)(DM-SO)(phen)] + (1) [21]. Tis complex (1) demonstrated a broad spectrum of antiproliferative activity toward several cancer cell lines and antimetastatic properties often superior to those exhibited by cisplatin [21][22][23]. Furthermore, (1) was also able to reduce glutathione (GSH) levels possibly as a specifc efect of the drug-induced stress [23].…”

“…This complex ( 1 ) demonstrated a broad spectrum of antiproliferative activity toward several cancer cell lines and antimetastatic properties often superior to those exhibited by cisplatin [ 21 – 23 ]. Furthermore, ( 1 ) was also able to reduce glutathione (GSH) levels possibly as a specific effect of the drug-induced stress [ 23 ]. This result was interesting, since GSH is the most abundant antioxidant in eukaryotic cells, showing particularly high levels in mitochondria, where it contributes to redox balance through ROS detoxification and phospholipidic membrane protection [ 45 ].…”

“…Particularly, on neuroblastoma cells, we observed a fast induction of mitochondrial apoptotic process and antimigratory capacity with respect to cisplatin [ 22 ]. Furthermore, 1 H-NMR-based metabolomics analyses allowed us to highlight an early alteration of glutathione (L- γ -glutamyl-L-cysteinyl-glycine; GSH) metabolism pathway compared to cisplatin [ 23 ], making this complex able to bypass cancer drug resistance related to GSH antioxidant system [ 24 ]. We also observed that the cytotoxic activity of this phenanthroline-containing compound can be optimized by modifying alkyl chain length since antiproliferative properties of platinum complexes can be influenced by molecular lipophilicity.…”

Chemomodulatory Effect of the Marine-Derived Metabolite “Terrein” on the Anticancer Properties of Gemcitabine in Colorectal Cancer Cells

“…Metabolomics is considered one of the best approaches to studying the effectiveness of drugs towards cancer [ 37 ] as well as assessing the reasons behind developing resistance toward drugs [ 38 ]. In this study, a metabolomic analysis has been conducted to compare the effect of terrein, gemcitabine, and a combination of both drugs on colorectal cells under normoxic as well as hypoxic conditions.…”