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

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 t...

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Main Authors:	Joanna L. Denbigh, David Perez-Guaita, Robbin R. Vernooij, Mark J. Tobin, Keith R. Bambery, Yun Xu, Andrew D. Southam, Farhat L. Khanim, Mark T. Drayson, Nicholas P. Lockyer, Royston Goodacre, Bayden R. Wood
Format:	Article
Language:	English
Published:	Nature Publishing Group 2017-06-01
Series:	Scientific Reports
Online Access:	https://doi.org/10.1038/s41598-017-02069-5

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record_format	Article
spelling	doaj-ac60fdf6ada446ecbc4c12809e9d41092020-12-08T00:43:58ZengNature Publishing GroupScientific Reports2045-23222017-06-017111210.1038/s41598-017-02069-5Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniquesJoanna L. Denbigh0David Perez-Guaita1Robbin R. Vernooij2Mark J. Tobin3Keith R. Bambery4Yun Xu5Andrew D. Southam6Farhat L. Khanim7Mark T. Drayson8Nicholas P. Lockyer9Royston Goodacre10Bayden R. Wood11Manchester Institute of Biotechnology and School of Chemistry, University of ManchesterCentre for Biospectroscopy and School of Chemistry, Monash UniversityCentre for Biospectroscopy and School of Chemistry, Monash UniversityAustralian SynchrotronAustralian SynchrotronManchester Institute of Biotechnology and School of Chemistry, University of ManchesterSchool of Biosciences, University of BirminghamSchool of Biosciences, University of BirminghamInstitute of Immunology and Immunotherapy, University of BirminghamManchester Institute of Biotechnology and School of Chemistry, University of ManchesterManchester Institute of Biotechnology and School of Chemistry, University of ManchesterCentre for Biospectroscopy and School of Chemistry, Monash UniversityAbstract 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.https://doi.org/10.1038/s41598-017-02069-5
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Joanna L. Denbigh David Perez-Guaita Robbin R. Vernooij Mark J. Tobin Keith R. Bambery Yun Xu Andrew D. Southam Farhat L. Khanim Mark T. Drayson Nicholas P. Lockyer Royston Goodacre Bayden R. Wood
spellingShingle	Joanna L. Denbigh David Perez-Guaita Robbin R. Vernooij Mark J. Tobin Keith R. Bambery Yun Xu Andrew D. Southam Farhat L. Khanim Mark T. Drayson Nicholas P. Lockyer Royston Goodacre Bayden R. Wood Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques Scientific Reports
author_facet	Joanna L. Denbigh David Perez-Guaita Robbin R. Vernooij Mark J. Tobin Keith R. Bambery Yun Xu Andrew D. Southam Farhat L. Khanim Mark T. Drayson Nicholas P. Lockyer Royston Goodacre Bayden R. Wood
author_sort	Joanna L. Denbigh
title	Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques
title_short	Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques
title_full	Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques
title_fullStr	Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques
title_full_unstemmed	Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques
title_sort	probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques
publisher	Nature Publishing Group
series	Scientific Reports
issn	2045-2322
publishDate	2017-06-01
description	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.
url	https://doi.org/10.1038/s41598-017-02069-5
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Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques

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