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

• DOI: 10.1186/s13045-018-0561-0
• Publication Date: 2018-02-20T00:30:11Z
• Authors: Thea Kristin Våts...; Marit Renée Myhre; Chloé Beate Steen; Sébastien Wälchli; Ole Christian Lin...; Baoyan Bai; Pierre Dillard; Theodossis A. The...; Toril Holien; Anders Sundan; Else Marit Inderberg; Erlend B. Smeland; June Helen Myklebust; Morten P. Oksvold
• Keywords: Artesunate; Dihydroartemisinin; B-cell lymphoma

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 previously been identified as growth suppressor in some cancer types was tested new treatment option lymphoma.We included sensitivity screen B cell lines. preclinical properties of single agent vitro 18 lines representing different histologies vivo aggressive xenograft model, using NSG mice. Artesunate-treated were analyzed by functional assays, gene expression profiling, protein identify the mechanism action.Drug screening highly potent anti-lymphoma drug. Artesunate induced suppression cells with IC50 comparable concentrations measured serum from artesunate-treated patients, while leaving normal B-cells unaffected. markedly inhibited tumor model. Gene analysis endoplasmic reticulum (ER) stress unfolded response affected pathways artesunate-induced ER markers ATF-4 DDIT3 specifically upregulated malignant B-cells, but not B-cells. In addition, significantly suppressed metabolism, affecting both respiration glycolysis.Artesunate demonstrated apoptosis-inducing effects across broad range vitro, prominent activity vivo, suggesting it be relevant lymphoma.