In vitro metabonomic study detects increases in UDP-GlcNAc and UDP-GalNAc, as early phase markers of cisplatin treatment response in brain tumor cells

Xiaoyan Pan, Martin Wilson, Ladan Mirbahai, Carmel McConville, Theodoros N. Arvanitis, Julian L. Griffin, Risto A. Kauppinen, Andrew C. Peet

    Research output: Contribution to journalArticlepeer-review

    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 1H nuclear magnetic resonance spectroscopy ( 1H 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 1H 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 1H 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. © 2011 American Chemical Society.
    Original languageEnglish
    Pages (from-to)3493-3500
    Number of pages7
    JournalJournal of Proteome Research
    Volume10
    Issue number8
    DOIs
    Publication statusPublished - 5 Aug 2011

    Keywords

    • 1H NMR
    • cell death
    • cisplatin
    • metabolomics
    • UDP-GalNAc
    • UDP-GlcNA

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