Detection of Metabolic Changes Induced via Drug Treatments in Live Cancer Cells and Tissue Using Raman Imaging Microscopy

Mioara Larion, Tyrone Dowdy, Victor Ruiz-Rodado, Matthew W. Meyer, Hua Song, Wei Zhang, Dionne Davis, Mark R. Gilbert, Adrian Lita

Research output: Contribution to journalArticle

Abstract

Isocitrate dehydrogenase 1 (IDH1) mutations in gliomas, fibrosarcoma, and other cancers leads to a novel metabolite, D-2-hydroxyglutarate, which is proposed to cause tumorigenesis. The production of this metabolite also causes vulnerabilities in cellular metabolism, such as lowering NADPH levels. To exploit this vulnerability, we treated glioma and fibrosarcoma cells that harbor an IDH1 mutation with an inhibitor of nicotinamide adenine dinucleotide (NAD⁺) salvage pathway, FK866, and observed decreased viability in these cells. To understand the mechanism of action by which the inhibitor FK866 works, we used Raman imaging microscopy and identified that proteins and lipids are decreased upon treatment with the drug. Raman imaging showed a different distribution of lipids throughout the cell in the presence of the drug compared with the untreated cells. We employed nuclear magnetic resonance NMR spectroscopy and mass spectrometry to identify the classes of lipids altered. Our combined analyses point to a decrease in cell division due to loss of lipid content that contributes to membrane formation in the in vitro setting. However, the FK866 drug did not have the same potency in vivo. The use of Raman imaging microscopy indicated an opposite trend of lipid distribution in the tissue collected from treated versus untreated mice when compared with the cells. These results demonstrate the role of Raman imaging microscopy to identify and quantify metabolic changes in cancer cells and tissue.

Original languageEnglish (US)
JournalBiosensors
Volume9
Issue number1
DOIs
StatePublished - Dec 28 2018

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Drug therapy
Microscopy
Microscopic examination
Cells
Tissue
Lipids
Imaging techniques
Isocitrate Dehydrogenase
Pharmaceutical Preparations
Fibrosarcoma
Neoplasms
Metabolites
Glioma
Magnetic Resonance Spectroscopy
Magnetic resonance spectroscopy
Salvaging
Mutation
Tissue Distribution
Ports and harbors
NADP

Keywords

  • fibrosarcoma IDH1
  • microscopy
  • NAD+ synthesis
  • Raman spectrometry
  • single cell imaging
  • tissue imaging

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Detection of Metabolic Changes Induced via Drug Treatments in Live Cancer Cells and Tissue Using Raman Imaging Microscopy. / Larion, Mioara; Dowdy, Tyrone; Ruiz-Rodado, Victor; Meyer, Matthew W.; Song, Hua; Zhang, Wei; Davis, Dionne; Gilbert, Mark R.; Lita, Adrian.

In: Biosensors, Vol. 9, No. 1, 28.12.2018.

Research output: Contribution to journalArticle

Larion, Mioara ; Dowdy, Tyrone ; Ruiz-Rodado, Victor ; Meyer, Matthew W. ; Song, Hua ; Zhang, Wei ; Davis, Dionne ; Gilbert, Mark R. ; Lita, Adrian. / Detection of Metabolic Changes Induced via Drug Treatments in Live Cancer Cells and Tissue Using Raman Imaging Microscopy. In: Biosensors. 2018 ; Vol. 9, No. 1.
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