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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2018

Open Access 01-12-2018 | Research

Artesunate shows potent anti-tumor activity in B-cell lymphoma

Authors: Thea Kristin Våtsveen, Marit Renée Myhre, Chloé Beate Steen, Sébastien Wälchli, Ole Christian Lingjærde, Baoyan Bai, Pierre Dillard, Theodossis A. Theodossiou, Toril Holien, Anders Sundan, Else Marit Inderberg, Erlend B. Smeland, June Helen Myklebust, Morten P. Oksvold

Published in: Journal of Hematology & Oncology | Issue 1/2018

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Abstract

Background

Although chemo-immunotherapy has led to an improved overall survival for most B-cell lymphoma types, relapsed and refractory disease remains a challenge. The malaria drug artesunate has previously been identified as a growth suppressor in some cancer types and was tested as a new treatment option in B-cell lymphoma.

Methods

We included artesunate in a cancer sensitivity drug screen in B lymphoma cell lines. The preclinical properties of artesunate was tested as single agent in vitro in 18 B-cell lymphoma cell lines representing different histologies and in vivo in an aggressive B-cell lymphoma xenograft model, using NSG mice. Artesunate-treated B lymphoma cell lines were analyzed by functional assays, gene expression profiling, and protein expression to identify the mechanism of action.

Results

Drug screening identified artesunate as a highly potent anti-lymphoma drug. Artesunate induced potent growth suppression in most B lymphoma cells with an IC50 comparable to concentrations measured in serum from artesunate-treated malaria patients, while leaving normal B-cells unaffected. Artesunate markedly inhibited highly aggressive tumor growth in a xenograft model. Gene expression analysis identified endoplasmic reticulum (ER) stress and the unfolded protein response as the most affected pathways and artesunate-induced expression of the ER stress markers ATF-4 and DDIT3 was specifically upregulated in malignant B-cells, but not in normal B-cells. In addition, artesunate significantly suppressed the overall cell metabolism, affecting both respiration and glycolysis.

Conclusions

Artesunate demonstrated potent apoptosis-inducing effects across a broad range of B-cell lymphoma cell lines in vitro, and a prominent anti-lymphoma activity in vivo, suggesting it to be a relevant drug for treatment of B-cell lymphoma.
Appendix
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Metadata
Title
Artesunate shows potent anti-tumor activity in B-cell lymphoma
Authors
Thea Kristin Våtsveen
Marit Renée Myhre
Chloé Beate Steen
Sébastien Wälchli
Ole Christian Lingjærde
Baoyan Bai
Pierre Dillard
Theodossis A. Theodossiou
Toril Holien
Anders Sundan
Else Marit Inderberg
Erlend B. Smeland
June Helen Myklebust
Morten P. Oksvold
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2018
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-018-0561-0

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