Preclinical activity of resazurin in acute myeloid leukaemia.

Ahead of Print

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 0372544 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2141 (Electronic) Linking ISSN: 00071048 NLM ISO Abbreviation: Br J Haematol Subsets: MEDLINE

Publication: Oxford : Wiley-Blackwell
Original Publication: Oxford : Blackwell Scientific Publications

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.)

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F-12148 Helse Vest; F-13102 Helse Vest; 182524 Kreftforeningen; 190175-2017 Kreftforeningen; 208012 Kreftforeningen; 303445 Kreftforeningen

Keywords: AML; optical imaging; preclinical; resazurin; therapy

Date Created: 20241125 Latest Revision: 20241125

20241126

10.1111/bjh.19872

39582120