Lymphoma and myeloma cells are highly sensitive to growth arrest and apoptosis induced by artesunate

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Abstract

Objectives:

The use of new drugs has improved the treatment of multiple myeloma and diffuse large B-cell lymphoma (DLBCL). Nevertheless, over time many patients relapse and develop resistance to treatment, and efforts are needed to overcome drug resistance. The widely used malaria drug artesunate has been reported to have antitumor activity, and we aimed to test the effects of artesunate on a panel of myeloma and lymphoma cells.

Methods:

Myeloma and DLBCL cell lines were treated with artesunate in vitro. The effects of artesunate treatment were evaluated using ATP content measurements for proliferation and annexin V/propidium iodide labeling for apoptosis. Western blotting was used to look for artesunate-induced protein changes. In addition, we measured artesunate effects on patient myeloma cells in the presence of bone marrow stromal cells.

Results:

Artesunate treatment efficiently inhibited cell growth and induced apoptosis in cell lines. Apoptosis was induced concomitantly with downregulation of MYC and anti-apoptotic Bcl-2 family proteins, as well as with cleavage of caspase-3. The IC50 values of artesunate in cell lines varied between 0.3 and 16.6 μm. Furthermore, some primary myeloma cells were also sensitive to artesunate at doses around 10 μm. Concentrations of this order are pharmacologically relevant as they can be obtained in plasma after intravenous administration of artesunate for malaria treatment.

Conclusion:

Our findings indicate that artesunate is a potential drug for treatment of multiple myeloma and DLBCL at doses of the same order as currently in use for treatment of malaria without serious adverse effects.

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