title: In vitro metabonomic study detects increases in UDP-GlcNAc and UDP-GalNAc, as early phase markers of cisplatin treatment response in brain tumor cells.
abstract: O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) is important in a number of biological processes and diseases including transcription, cell stress, diabetes, and neurodegeneration and may be a marker of tumor metastasis. Uridine diphospho-N-acetylglucosamine (UDP-GlcNAc), the donor molecule in O-GlcNAcylation, can be detected by (1)H nuclear magnetic resonance spectroscopy ((1)H NMR), giving the potential to measure its level noninvasively, providing a novel biomarker of prognosis and treatment monitoring. In this in vitro metabonomic study, four brain cancer cell lines were exposed to cisplatin and studied for metabolic responses using (1)H NMR. The Alamar blue assay and DAPI staining were used to assess cell sensitivity to cisplatin treatment and to confirm cell death. It is shown that in the cisplatin responding cells, UDP-GlcNAc and uridine diphospho-N-acetylgalactosamine (UDP-GalNAc), in parallel with (1)H NMR detected lipids, increased with cisplatin exposure before or at the onset of the microscopic signs of evolving cell death. The changes in UDP-GlcNAc and UDP-GalNAc were not detected in the nonresponders. These glycosylated UDP compounds, the key substrates for glycosylation of proteins and lipids, are commonly implicated in cancer proliferation and malignant transformation. However, the present study mechanistically links UDP-GlcNAc and UDP-GalNAc to cancer cell death following chemotherapeutic treatment.
authors.affiliation: Cancer Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Pan
authors.forename: Martin
authors.initials: M
authors.lastname: Wilson
authors.forename: Ladan
authors.initials: L
authors.lastname: Mirbahai
authors.forename: Carmel
authors.initials: C
authors.lastname: McConville
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Arvanitis
authors.forename: Julian L
authors.initials: JL
authors.lastname: Griffin
authors.forename: Risto A
authors.initials: RA
authors.lastname: Kauppinen
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Peet
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics; D008991:Monitoring, Physiologic; D011379:Prognosis; D051381:Rats; D014536:Uridine Diphosphate N-Acetylgalactosamine / Q000378:metabolism*; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D014537:Uridine Diphosphate N-Acetylglucosamine; D014536:Uridine Diphosphate N-Acetylgalactosamine; D002945:Cisplatin