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British Journal of Pharmacology

British Journal of Pharmacology

IF: 6.8
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Artesunate, a new antimalarial clinical?drug, exhibits potent anti-AML activity by targeting the ROS/Bim and TFRC/Fe2+ pathways

Published:11 November 2022 DOI: 10.1111/bph.15986
Yi Liu, Han Li, Zhihong Luo, You Yu, Jingzhao Yang, Min Zhang, Betty Yuen Kwan Law, Zan Huang, Wenhua Li

Abstract

Background and Purpose

Artesunate, approved by the Food and Drug Administration in 2020 as a new treatment for severe malaria, also shows anti-tumour activity against acute myeloid leukaemia (AML). However, the underlying molecular mechanism(s) of artesunate-induced apoptosis and differentiation of AML is not clearly elucidated.

Experimental Approach

The biological effects of artesunate on AML were explored in vitro, using cells from AML patients and leukaemia cell lines, and in vivo, using female C57BL/6 or nude nu/nu BALB/c mice. Underlying mechanisms in vitro were examined with the Trypan blue dye exclusion assay, western blotting and flow cytometry. Effects of artesunate in C57BL/6 mice intravenously injected with murine AML cells (C1498-GFP) were assessed by numbers of AML cells and by survival.

Key Results

In vitro, artesunate promoted apoptosis and differentiation in both leukaemia cell lines and patient-derived primary leukaemia cells. Mechanistically, artesunate promoted cell apoptosis by triggering reactive oxygen species (ROS) production and increasing expression of the pro-apoptotic protein Bim. Interestingly, transferrin receptor 1 (TFRC)-mediated regulation of intracellular iron homeostasis also played an essential role in AML cell differentiation induced by artesunate. In vivo, artesunate slowed AML progression and prolonged survival in a mouse leukaemia model. Notably, artesunate displayed no apparent toxicity towards healthy haematopoietic stem cells, bone marrow mononuclear cells or experimental animals.

Conclusion and Implications

Artesunate is a safe agent with significant anti-leukaemia effects in mice and may serve as a promising chemotherapeutic strategy for patients with AML, based on two different mechanisms, targeting the ROS/Bim and the TFRC/Fe2+ pathways.

Substances (36)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Artemisinin 63968-64-9 C15H22O5 860 suppliers $5.00-$2700.00
Artemisinin 63968-64-9 C15H22O5 860 suppliers $5.00-$2700.00
Artemisinin 63968-64-9 C15H22O5 860 suppliers $5.00-$2700.00
Artemisinin 63968-64-9 C15H22O5 860 suppliers $5.00-$2700.00
Artesunate 88495-63-0 C19H28O8 712 suppliers $5.00-$2670.00
Artesunate 88495-63-0 C19H28O8 712 suppliers $5.00-$2670.00
Artesunate 88495-63-0 C19H28O8 712 suppliers $5.00-$2670.00
Artesunate 88495-63-0 C19H28O8 712 suppliers $5.00-$2670.00
Artemether 71963-77-4 C16H26O5 684 suppliers $13.00-$4200.00
Artemether 71963-77-4 C16H26O5 684 suppliers $13.00-$4200.00

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