Preclinical activity of resazurin in acute myeloid leukaemia.

Autor: Ha TQ; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway., Andresen V; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.; K.G. Jebsen Centre for Myeloid Blood Cancer, Department of Clinical Science, University of Bergen, Bergen, Norway., Erikstein BS; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.; K.G. Jebsen Centre for Myeloid Blood Cancer, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway., Popa M; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.; KinN Therapeutics AS, Bergen, Norway., Gullaksen SE; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway.; K.G. Jebsen Centre for Myeloid Blood Cancer, Department of Clinical Science, University of Bergen, Bergen, Norway., Reikvam H; Department of Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway.; K.G. Jebsen Centre for Myeloid Blood Cancer, Department of Clinical Science, University of Bergen, Bergen, Norway.; Leukemia Research Group, Department of Clinical Science, University of Bergen, Bergen, Norway., McCormack E; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway.; K.G. Jebsen Centre for Myeloid Blood Cancer, Department of Clinical Science, University of Bergen, Bergen, Norway.; Centre for Pharmacy, Department of Clinical Science, University of Bergen, Bergen, Norway., Gjertsen BT; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway.; K.G. Jebsen Centre for Myeloid Blood Cancer, Department of Clinical Science, University of Bergen, Bergen, Norway.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2024 Nov 24. Date of Electronic Publication: 2024 Nov 24.
DOI: 10.1111/bjh.19872
Abstrakt: Resazurin, a phenoxazine used in cell viability assays, acts in vitro as an anti-leukaemic compound through the production of cellular reactive oxygen species (ROS) resulting in mitochondrial dysfunction and cell death. However, the in vivo tolerance and efficacy of resazurin in cancer are unknown. In this study, we investigated the in vitro and in vivo effects of resazurin in acute myeloid leukaemia (AML). Resazurininduced cell death in a dose-dependent manner in AML cell lines and reduced proliferation and colony formation in ex vivo treated patient-derived AML cells. Cells treated with a reduced dose of resazurin for 72 h acquired a more mature immunophenotype suggesting cell differentiation as a mechanism contributing to the anti-leukaemic effect. In vivo optical imaging in healthy mice demonstrated a reduction of resazurin to resorufin within 30 min and non-detectable after 2 h, supporting dosing twice daily as optimal. In subcutaneous and orthotopic models of MV4-11 AML in NOD/SCID IL2rγ null mice, anti-tumour effects and an increased survival were found at a dose level of 75 mg/kg twice daily without observed toxicity. Our results suggest that resazurin represents a novel experimental therapeutic for the treatment of AML.
(© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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