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Biosensors 2019, 9(1), 5; https://doi.org/10.3390/bios9010005

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

1
Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
2
ThermoFisher Scientific, 5225 Verona Road, Madison, WI 53711, USA
*
Author to whom correspondence should be addressed.
Received: 19 October 2018 / Revised: 16 December 2018 / Accepted: 24 December 2018 / Published: 28 December 2018
(This article belongs to the Special Issue Applications of Raman Techniques in Biosensing)
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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. View Full-Text
Keywords: fibrosarcoma IDH1; NAD+ synthesis; Raman spectrometry; microscopy; single cell imaging; tissue imaging fibrosarcoma IDH1; NAD+ synthesis; Raman spectrometry; microscopy; single cell imaging; tissue imaging
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Larion, M.; Dowdy, T.; Ruiz-Rodado, V.; Meyer, M.W.; Song, H.; Zhang, W.; Davis, D.; Gilbert, M.R.; Lita, A. Detection of Metabolic Changes Induced via Drug Treatments in Live Cancer Cells and Tissue Using Raman Imaging Microscopy. Biosensors 2019, 9, 5.

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