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1.
Molecules ; 25(7)2020 Apr 03.
Article in English | MEDLINE | ID: mdl-32260207

ABSTRACT

It is known that intake of dietary fatty acid (FA) is strongly correlated with prostate cancer progression but is highly dependent on the type of FAs. High levels of palmitic acid (PA) or arachidonic acid (AA) can stimulate the progression of cancer. In this study, a unique experimental set-up consisting of a Raman microscope, coupled with a commercial shear-flow microfluidic system is used to monitor fatty acid uptake by prostate cancer (PC-3) cells in real-time at the single cell level. Uptake of deuterated PA, deuterated AA, and the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were monitored using this new system, while complementary flow cytometry experiments using Nile red staining, were also conducted for the validation of the cellular lipid uptake. Using this novel experimental system, we show that DHA and EPA have inhibitory effects on the uptake of PA and AA by PC-3 cells.


Subject(s)
Arachidonic Acid/analysis , Fatty Acids, Omega-3/pharmacology , Palmitic Acid/analysis , Prostatic Neoplasms/chemistry , Docosahexaenoic Acids/pharmacology , Eicosapentaenoic Acid/pharmacology , Humans , Male , Microfluidics , PC-3 Cells , Single-Cell Analysis , Spectrum Analysis, Raman
2.
Sci Rep ; 7(1): 2649, 2017 06 01.
Article in English | MEDLINE | ID: mdl-28572622

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/chemistry , Bezafibrate/chemistry , Bezafibrate/pharmacology , Leukemia, Myeloid, Acute/drug therapy , Medroxyprogesterone/chemistry , Antineoplastic Combined Chemotherapy Protocols/pharmacology , HL-60 Cells , Humans , Medroxyprogesterone/pharmacology , Spectroscopy, Fourier Transform Infrared , Spectrum Analysis, Raman , Synchrotrons
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