Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques

Research output: Contribution to journalArticle

Authors

  • Joanna L. Denbigh
  • David Perez-Guaita
  • Robbin R. Vernooij
  • Mark J. Tobin
  • Keith R. Bambery
  • Yun Xu
  • Nicholas P. Lockyer
  • Royston Goodacre
  • Bayden R. Wood

Colleges, School and Institutes

External organisations

  • University of Manchester
  • Biomedical Research Centre, School of Environment and Life Sciences, University of Salford
  • Centre for Biospectroscopy and School of Chemistry, Monash University
  • Australian Synchrotron

Abstract

Acute myeloid leukaemia (AML) is a life threatening cancer for which there is an urgent clinical need for novel therapeutic approaches. A redeployed drug combination of bezafibrate and medroxyprogesterone acetate (BaP) has shown anti-leukaemic activity in vitro and in vivo. Elucidation of the BaP mechanism of action is required in order to understand how to maximise the clinical benefit. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, Synchrotron radiation FTIR (S-FTIR) and Raman microspectroscopy are powerful complementary techniques which were employed to probe the biochemical composition of two AML cell lines in the presence and absence of BaP. Analysis was performed on single living cells along with dehydrated and fixed cells to provide a large and detailed data set. A consideration of the main spectral differences in conjunction with multivariate statistical analysis reveals a significant change to the cellular lipid composition with drug treatment; furthermore, this response is not caused by cell apoptosis. No change to the DNA of either cell line was observed suggesting this combination therapy primarily targets lipid biosynthesis or effects bioactive lipids that activate specific signalling pathways.

Details

Original languageEnglish
Article number2649
JournalScientific Reports
Volume7
Publication statusPublished - 1 Jun 2017

Keywords

  • Journal Article, infrared spectroscopy , lipids