Metabolomics Analysis Revealed Significant Metabolic Changes in Brain Cancer Cells Treated with Paclitaxel and/or Etoposide

• Published in: International journal of molecular sciences Vol. 23; no. 22; p. 13940
• Main Authors: Semreen, Ahlam M, Alsoud, Leen Oyoun, El-Huneidi, Waseem, Ahmed, Munazza, Bustanji, Yasser, Abu-Gharbieh, Eman, El-Awady, Raafat, Ramadan, Wafaa S, Alqudah, Mohammad A Y, Shara, Mohd, Abuhelwa, Ahmad Y, Soares, Nelson C, Semreen, Mohammad H, Alzoubi, Karem H
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.11.2022; MDPI
• Subjects: Adenosine; Antitumor activity; Arginine; Biomarkers; Brain cancer; Brain Neoplasms - drug therapy; Brain research; Cancer; Cancer therapies; Central nervous system; Citric acid; Disease; Etoposide; Etoposide - pharmacology; Glioblastoma; High performance liquid chromatography; Humans; Hypoxanthine; Mass spectrometry; Mass spectroscopy; Medical research; Metabolic pathways; Metabolism; Metabolites; Metabolomics; Mevalonic acid; Paclitaxel; Paclitaxel - pharmacology; Pathogenesis; Phenylalanine; Polyamines; Quadrupoles; Scientific imaging; Spectrometry, Mass, Electrospray Ionization - methods; Tandem Mass Spectrometry - methods; U373; U87; untargeted metabolomics; paclitaxel; untargeted metabolomics; glioblastoma; U87; etoposide; U373; metabolites; UHPLC-ESI-QTOF-MS; metabolic pathways
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232213940

Cancer of the central nervous system (CNS) is ranked as the 19th most prevalent form of the disease in 2020. This study aims to identify candidate biomarkers and metabolic pathways affected by paclitaxel and etoposide, which serve as potential treatments for glioblastoma, and are linked to the pathogenesis of glioblastoma. We utilized an untargeted metabolomics approach using the highly sensitive ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) for identification. In this study, 92 and 94 metabolites in U87 and U373 cell lines were profiled, respectively. The produced metabolites were then analyzed utilizing -tests, volcano plots, and enrichment analysis modules. Our analysis revealed distinct metabolites to be significantly dysregulated (nutriacholic acid, L-phenylalanine, L-arginine, guanosine, ADP, hypoxanthine, and guanine), and to a lesser extent, mevalonic acid in paclitaxel and/or etoposide treated cells. Furthermore, both urea and citric acid cycles, and metabolism of polyamines and amino acids (aspartate, arginine, and proline) were significantly enriched. These findings can be used to create a map that can be utilized to assess the antitumor effect of paclitaxel and/or etoposide within the studied cancer cells.