Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques.
Joanna L DenbighDavid Perez-GuaitaRobbin R VernooijMark J TobinKeith R BamberyYun XuAndrew D SouthamFarhat L KhanimMark T DraysonNicholas P LockyerRoyston GoodacreBayden R WoodPublished in: Scientific reports (2017)
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.
Keyphrases
- single molecule
- living cells
- combination therapy
- acute myeloid leukemia
- fluorescent probe
- single cell
- drug induced
- induced apoptosis
- high resolution
- fatty acid
- liver failure
- molecular dynamics simulations
- cell proliferation
- optical coherence tomography
- stem cells
- rna seq
- adverse drug
- allogeneic hematopoietic stem cell transplantation
- data analysis
- emergency department
- circulating tumor
- electronic health record
- high throughput
- dendritic cells
- squamous cell carcinoma
- machine learning
- respiratory failure
- radiation induced
- cell death
- dna damage
- big data
- cell free
- oxidative stress
- dna damage response
- label free
- replacement therapy
- immune response
- raman spectroscopy
- lymph node metastasis