title: Highlighting a need to distinguish cell cycle signatures from cellular responses to chemotherapeutics in SR-FTIR spectroscopy.
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 G(1), S or G(2)/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.
authors.affiliation: Manchester Interdisciplinary Biocentre, University of Manchester, 131 Princess Street, Manchester, UK M1 7DN.
authors.forename: C
authors.initials: C
authors.lastname: Hughes
authors.forename: M D
authors.initials: MD
authors.lastname: Brown
authors.forename: F J
authors.initials: FJ
authors.lastname: Ball
authors.forename: G
authors.initials: G
authors.lastname: Monjardez
authors.forename: N W
authors.initials: NW
authors.lastname: Clarke
authors.forename: K R
authors.initials: KR
authors.lastname: Flower
authors.forename: P
authors.initials: P
authors.lastname: Gardner
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D025341:Principal Component Analysis; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D005472:Fluorouracil