Pseudotargeted metabolomics method and its application in erastin-stimulated gastric adenocarcinoma cells based on liquid chromatography with tandem mass spectrometry

• Published in: International journal of mass spectrometry Vol. 500; p. 117238
• Main Authors: Liu, Ying, Hu, Wenchao, Asmamaw, Mogesdessale, Pan, Lulu, Liu, Hongmin, Li, Juan
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.06.2024
• Subjects: Erastin; Gastric cancer; LC-MS/MS; Metabolomics; MGC-803 cells; Pseudotargeted method; Pseudotargeted method; Metabolomics; LC-MS/MS; Erastin; MGC-803 cells; Gastric cancer
• ISSN: 1387-3806; 1873-2798
• DOI: 10.1016/j.ijms.2024.117238

Erastin, a classical ferroptosis inducer, exerts cytotoxicity in several types of cancer cells including gastric cancer cells. However, the mechanism of erastin in regulating metabolic pathways in gastric cancer remains largely unclear. To investigate the gastric cellular response to erastin therapy, a pseudotargeted metabolomics method was achieved on ultra-high performance liquid chromatography-hybrid triple quadrupole linear ion trap mass spectrometry (UHPLC-QTRAP MS), which was used to investigate metabolic changes between erastin-treated MGC-803 cells and the controls at different time points. We found that erastin induced tremendous impact on the metabolome of gastric cells by affecting key metabolic processes, such as cysteine and methionine metabolism, tryptophan metabolism, purine metabolism, glutathione biosynthesis, glycolysis and TCA cycle. Interestingly, S-adenosylmethionine, methionine, serine and cysteine were obviously increasing treads after erastin treatment, while S-adenosylhomocysteine and glutathione were always down-regulated up to 24 h. The results indicated that DNA methylation was activated and glutathione biosynthesis was blocked in erastin-treated MGC-803 gastric cells, highlighting the importance of erastin as a promising drug candidate for in vivo treatment of gastric tumor. [Display omitted] •A pseudotargeted metabolomics method based on LC-MS/MS to analyze cell samples.•The developed method achieved satisfactory repeatability and high sensitivity.•A total of 278 metabolites were determined for exploring metabolic changes in erastin-induced MGC-803 cells.