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Issue 24, 2012
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Highlighting a need to distinguish cell cycle signatures from cellular responses to chemotherapeutics in SR-FTIR spectroscopy

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Abstract

Previous research has seen difficulties in establishing clear discrimination by principal component analysis (PCA) between drug-treated cells analysed by single point SR-FTIR spectroscopy, relative to multisampling cell monolayers by conventional FTIR. It is suggested that the issue arises due to signal mixing between cellular-response signatures and cell cycle phase contributions in individual cells. Consequently, chemometric distinction of cell spectra treated with multiple drugs is difficult even with supervised methods. In an effort to separate cell cycle chemistry from cellular response chemistry in the spectra, renal carcinoma cells were stained with propidium iodide and fluorescent-activated cell sorted (FACS) after exposure to a number of chemotherapeutic compounds; 5-fluorouracil (5FU) and a set of novel gold-based experimental compounds. The cell spectra were analysed separately by PCA in G1, S or G2/M phase. The mode of action of established drug 5FU, known to disrupt S phase, was confirmed by FACS analysis. The chemical signature of 5FU-treated cells discriminated against both the control and gold-compound (KF0101)-treated cell spectra, suggesting a different mode of action due to a difference in cellular response.

Graphical abstract: Highlighting a need to distinguish cell cycle signatures from cellular responses to chemotherapeutics in SR-FTIR spectroscopy

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Publication details

The article was received on 14 May 2012, accepted on 10 Oct 2012 and first published on 11 Oct 2012


Article type: Paper
DOI: 10.1039/C2AN35633C
Citation: Analyst, 2012,137, 5736-5742
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    Highlighting a need to distinguish cell cycle signatures from cellular responses to chemotherapeutics in SR-FTIR spectroscopy

    C. Hughes, M. D. Brown, F. J. Ball, G. Monjardez, N. W. Clarke, K. R. Flower and P. Gardner, Analyst, 2012, 137, 5736
    DOI: 10.1039/C2AN35633C

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