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.
Highlights
Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques
Cells analysed by ATR-Fourier Transform infrared (FTIR) were sampled from a heterogeneous cell pellet which predominately consisted of viable cells, but was likely to contain cells in varying stages of necrosis and cell debris from cells which may have undergone
All three spectroscopic techniques employed in this study revealed an increase in the CH2:CH3 ratio of lipid peaks in the high wavenumber spectral region of drug treated cells which indicates a change in cellular lipid saturation state with bezafibrate and medroxyprogesterone acetate (BaP) treatment and demonstrates good consistency between the analytical techniques
Summary
Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques. Full text material held in the repository is made freely available online and can be read, downloaded and copied for non-commercial private study or research purposes. OPEN Probing the action of a novel anti-leukaemic drug therapy at the single cell level using. 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. 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. Patients can die from impaired haemopoiesis within weeks of diagnosis and responses to current treatments and overall survival of patients post-treatment generally remains poor[1]
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