dc.contributor.author | Våtsveen, Thea K | |
dc.contributor.author | Myhre, Marit R | |
dc.contributor.author | Steen, Chloé B | |
dc.contributor.author | Wälchli, Sébastien | |
dc.contributor.author | Lingjærde, Ole C | |
dc.contributor.author | Bai, Baoyan | |
dc.contributor.author | Dillard, Pierre | |
dc.contributor.author | Theodossiou, Theodossis A | |
dc.contributor.author | Holien, Toril | |
dc.contributor.author | Sundan, Anders | |
dc.contributor.author | Inderberg, Else M | |
dc.contributor.author | Smeland, Erlend B | |
dc.contributor.author | Myklebust, June H | |
dc.contributor.author | Oksvold, Morten P | |
dc.date.accessioned | 2018-02-20T06:00:25Z | |
dc.date.available | 2018-02-20T06:00:25Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Journal of Hematology & Oncology. 2018 Feb 20;11(1):23 | |
dc.identifier.uri | http://hdl.handle.net/10852/60258 | |
dc.description.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. | |
dc.language.iso | eng | |
dc.rights | The Author(s); licensee BioMed Central Ltd. | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.title | Artesunate shows potent anti-tumor activity in B-cell lymphoma | |
dc.type | Journal article | |
dc.date.updated | 2018-02-20T06:00:25Z | |
dc.creator.author | Våtsveen, Thea K | |
dc.creator.author | Myhre, Marit R | |
dc.creator.author | Steen, Chloé B | |
dc.creator.author | Wälchli, Sébastien | |
dc.creator.author | Lingjærde, Ole C | |
dc.creator.author | Bai, Baoyan | |
dc.creator.author | Dillard, Pierre | |
dc.creator.author | Theodossiou, Theodossis A | |
dc.creator.author | Holien, Toril | |
dc.creator.author | Sundan, Anders | |
dc.creator.author | Inderberg, Else M | |
dc.creator.author | Smeland, Erlend B | |
dc.creator.author | Myklebust, June H | |
dc.creator.author | Oksvold, Morten P | |
dc.identifier.cristin | 1596236 | |
dc.identifier.doi | http://dx.doi.org/10.1186/s13045-018-0561-0 | |
dc.identifier.urn | URN:NBN:no-62916 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/60258/1/13045_2018_Article_561.pdf | |
dc.type.version | PublishedVersion | |
cristin.articleid | 23 | |