De Castro Federica, Stefàno Erika, De Luca Erik, Muscella Antonella, Marsigliante Santo, Benedetti Michele, Fanizzi Francesco Paolo
Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Via Monteroni, I-73100 Lecce, Italy.
Bioinorg Chem Appl. 2022 Jun 10;2022:8932137. doi: 10.1155/2022/8932137. eCollection 2022.
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-CHOMe)(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 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.
基于核磁共振的代谢组学是一种非常有效的工具,通过深入了解药物的作用模式来评估肿瘤对药物的反应。最近,合成了一种新型的铂(II)配合物[Pt(ƞ-CHOMe)(DMSO)(phen)](phen = 1,10-菲咯啉),即Pt-EtOMeSOphen,并研究了其对八种人类癌细胞系的抗肿瘤活性。在大多数癌细胞系中,尤其是对神经母细胞瘤细胞系(SH-SY5Y),Pt-EtOMeSOphen显示出比顺铂更高的细胞毒性作用。在本研究中,使用基于氢核磁共振的代谢组学研究了Pt-EtOMeSOphen对SH-SY5Y细胞的作用机制,并与顺铂进行了比较。观察到的SH-SY5Y细胞在治疗下的时间反应表明,与顺铂相比,Pt-EtOMeSOphen的作用更快,在暴露六小时后就已观察到反应,提示存在胞质靶点。基于核磁共振的代谢组学证明了谷胱甘肽代谢途径和二酰基甘油表达的特殊改变。