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

Joanna Denbigh; David Perez-Guaita; Robbin Vernooij; Mark J. Tobin; Keith R. Bambery; Yun Xu; Andrew D. Southam; Farhat L. Khanim; Mark T. Drayson; Nicholas Lockyer; Royston Goodacre; Bayden R. Wood

doi:10.1038/s41598-017-02069-5

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

Joanna Denbigh, David Perez-Guaita, Robbin Vernooij, Mark J. Tobin, Keith R. Bambery, Yun Xu, Andrew D. Southam, Farhat L. Khanim, Mark T. Drayson, Nicholas Lockyer, Royston Goodacre, Bayden R. Wood

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	Scientific Reports
Volume	7
Early online date	1 Jun 2017
DOIs	https://doi.org/10.1038/s41598-017-02069-5
Publication status	Published - 2017

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Denbigh, J., Perez-Guaita, D., Vernooij, R., Tobin, M. J., Bambery, K. R., Xu, Y., Southam, A. D., Khanim, F. L., Drayson, M. T., Lockyer, N., Goodacre, R., & Wood, B. R. (2017). Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques. Scientific Reports, 7. https://doi.org/10.1038/s41598-017-02069-5

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title = "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 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.",

author = "Joanna Denbigh and David Perez-Guaita and Robbin Vernooij and Tobin, {Mark J.} and Bambery, {Keith R.} and Yun Xu and Southam, {Andrew D.} and Khanim, {Farhat L.} and Drayson, {Mark T.} and Nicholas Lockyer and Royston Goodacre and Wood, {Bayden R.}",

year = "2017",

doi = "10.1038/s41598-017-02069-5",

language = "English",

volume = "7",

journal = "Scientific Reports",

issn = "2045-2322",

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T1 - Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques

AU - Denbigh, Joanna

AU - Perez-Guaita, David

AU - Vernooij, Robbin

AU - Tobin, Mark J.

AU - Bambery, Keith R.

AU - Xu, Yun

AU - Southam, Andrew D.

AU - Khanim, Farhat L.

AU - Drayson, Mark T.

AU - Lockyer, Nicholas

AU - Goodacre, Royston

AU - Wood, Bayden R.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-017-02069-5

DO - 10.1038/s41598-017-02069-5

M3 - Article

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

ER -

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

Abstract

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