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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ac60fdf6ada446ecbc4c12809e9d4109
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spelling	oai:doaj.org-article:ac60fdf6ada446ecbc4c12809e9d41092021-12-02T12:30:45ZProbing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques10.1038/s41598-017-02069-52045-2322https://doaj.org/article/ac60fdf6ada446ecbc4c12809e9d41092017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02069-5https://doaj.org/toc/2045-2322Abstract 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.Joanna L. DenbighDavid Perez-GuaitaRobbin R. VernooijMark J. TobinKeith R. BamberyYun XuAndrew D. SouthamFarhat L. KhanimMark T. DraysonNicholas P. LockyerRoyston GoodacreBayden R. WoodNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
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 Portfolio
publishDate	2017
url	https://doaj.org/article/ac60fdf6ada446ecbc4c12809e9d4109
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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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