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Lipid biomarkers of glioma cell growth arrest and cell death detected by 1H magic angle spinning MRS

Mirbahai, Ladan, Wilson, Martin, Shaw, Christopher S., McConville, Carmel, Malcomson, Roger D.G., Kauppinen, Risto A. and Peet, Andrew C. 2012, Lipid biomarkers of glioma cell growth arrest and cell death detected by 1H magic angle spinning MRS, NMR in biomedicine, vol. 25, no. 11, pp. 1253-1262, doi: 10.1002/nbm.2796.

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Title Lipid biomarkers of glioma cell growth arrest and cell death detected by 1H magic angle spinning MRS
Formatted title Lipid biomarkers of glioma cell growth arrest and cell death detected by 1H magic angle spinning MRS
Author(s) Mirbahai, Ladan
Wilson, Martin
Shaw, Christopher S.ORCID iD for Shaw, Christopher S. orcid.org/0000-0003-1499-0220
McConville, Carmel
Malcomson, Roger D.G.
Kauppinen, Risto A.
Peet, Andrew C.
Journal name NMR in biomedicine
Volume number 25
Issue number 11
Start page 1253
End page 1262
Total pages 10
Publisher Wiley
Place of publication Chichester, Eng.
Publication date 2012-11
ISSN 1099-1492
Keyword(s) biomarkers
cell growth arrest
apoptosis
lipid alterations
lipid droplets
1H magic angle spinning NMR spectroscopy
Animals
Annexin A5
Biomarkers, Tumor
Brain Neoplasms
Cell Cycle
Cell Death
Cell Line, Tumor
Cell Proliferation
Cisplatin
DNA Fragmentation
Flow Cytometry
Fluorescein-5-isothiocyanate
Glioma
Indoles
Lipids
Magnetic Resonance Spectroscopy
Oxazines
Propidium
Protons
Rats
Staining and Labeling
Trypan Blue
Summary Biomarkers of early response to treatment have the potential to improve cancer therapy by allowing treatment to be tailored to the individual. Alterations in lipids detected by in vivo MRS have been suggested as noninvasive biomarkers of cell stress and early indicators of cell death. An improved understanding of the relationship between MRS lipids and cell stress in vitro would aid in the translation of this technique into clinical use. Rat BT4C glioma cells were treated with 50 µm cis-dichlorodiammineplatinum II (cisplatin), a commonly used chemotherapeutic agent, and harvested at several time points up to 72 h. High-resolution magic angle spinning 1H MRS of cells was then performed on a 600-MHz NMR spectrometer. The metabolites were quantified using a time domain fitting method, TARQUIN. Increases were detected in saturated and polyunsaturated fatty acid resonances early during the exposure to cisplatin. The fatty acid CH2/CH3 ratio was unaltered by treatment after allowing for contributions of macromolecules. Polyunsaturated fatty acids increased on treatment, with the group -CH=CH-CH2-CH=CH- accounting for all the unsaturated fatty acid signals. Transmission electron microscopy, in addition to Nile red and 4',6-diamino-2-phenylindole co-staining, revealed that the lipid increase was associated with cytoplasmic neutral lipid droplets. Small numbers of apoptotic and necrotic cells were detected by trypan blue, annexin V-fluorescein isothiocyanate-labelled flow cytometry and DNA laddering after up to 48 h of cisplatin exposure. Propidium iodide flow cytometry revealed that cells accumulated in the G1 stage of the cell growth cycle. In conclusion, an increase in the size of the lipid droplets is detected in morphologically viable cells during cisplatin exposure. 1H MRS can detect lipid alterations during cell cycle arrest and progression of cell death, and has the potential to provide a noninvasive biomarker of treatment efficacy in vivo.
Language eng
DOI 10.1002/nbm.2796
Field of Research 111204 Cancer Therapy (excl Chemotherapy and Radiation Therapy)
1103 Clinical Sciences
0304 Medicinal And Biomolecular Chemistry
0903 Biomedical Engineering
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2012, Wiley
Persistent URL http://hdl.handle.net/10536/DRO/DU:30089573

Document type: Journal Article
Collections: Faculty of Health
School of Exercise and Nutrition Sciences
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