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The contradictory role of febuxostat in ABCG2 expression and potentiating hypericin-mediated photodynamic therapy in colorectal cancers

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Abstract

Photodynamic Therapy (PDT) is an emerging method to treat colorectal cancers (CRC). Hypericin (HYP) is an effective mediator of PDT and the ABCG2 inhibitor, Febuxostat (FBX) could augment PDT. HT29 and HEK293 cells showed light dependant cytotoxic response to PDT in both 2D and 3D cell models. FBX co-treatment was not found to improve PDT cytotoxicity. Next, ABCG2 protein expression was observed in HT29 but not in HEK293 cells. However, ABCG2 gene expression analysis did not support protein expression results as ABCG2 gene expression results were found to be higher in HEK293 cells. Although HYP treatment was found to significantly reduce ABCG2 gene expression levels in both cell lines, FBX treatment partially restored ABCG2 gene expression. Our findings indicate that FBX co-treatment may not be suitable for augmenting HYP-mediated PDT in CRC but could potentially be useful for other applications.

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Data availability

Data will be made available on request.

Abbreviations

PDT:

Photodynamic Therapy

CRC:

Colorectal cancers

HYP:

Hypericin

FBX:

Febuxostat

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Funding

The study is funded by the National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Centre (BRC). The views expressed in this study are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health. This work was also supported by a Royal Society International Exchanges Award (IEC\R3\203014) to D.G.J and M.I.K., a UKRI EPSRC Research Programme Grant (753910/B19R13527) and Bowel Cancer UK/RCS Eng Colorectal Research Chair Award (18SC0001) to D.G.J.

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Authors and Affiliations

  1. School of Medicine, University of Leeds, St James University Hospital, Leeds, LS9 7TF, UK

    Aaron King, Thomas Maisey, Erica L. Harris, James A. Poulter, David G. Jayne & M. Ibrahim Khot

  2. School of Chemistry and Biosciences, University of Bradford, Bradford, BD7 1DP, UK

    M. Ibrahim Khot

  3. Richmond Building, School of Chemistry and Biosciences, Faculty of Life Sciences, University of Bradford, Bradford, BD7 1DP, UK

    M. Ibrahim Khot

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  1. Aaron King
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Contributions

D.G.J. and M.I.K. created the research project and conceptualised the study. A.K. performed the experiments. T.M. and E.H. provided technical and experimental supervision. A.K., M.I.K. and J.L.P. analysed the results. M.I.K. wrote and edited the manuscript. All authors approve of the final manuscript.

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Correspondence to M. Ibrahim Khot.

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King, A., Maisey, T., Harris, E.L. et al. The contradictory role of febuxostat in ABCG2 expression and potentiating hypericin-mediated photodynamic therapy in colorectal cancers. Photochem Photobiol Sci (2024). https://doi.org/10.1007/s43630-024-00575-w

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