Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

J Hematol Oncol. 2018 02 20 ;11(1):23. Epub 2018 Feb 20. PMID: 29458389

Abstract Author(s):

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

Article Affiliation:

Thea Kristin Våtsveen


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 ICcomparable 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.

Study Type : Animal Study, In Vitro Study
Additional Links
Pharmacological Actions : Apoptotic : CK(6986) : AC(5304)

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Sayer Ji
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