Artesunate possesses anti-leukemia properties that can be enhanced by arsenic trioxide

Abstract

Artesunate (ART), an effective and safe anti-malaria drug, also exhibits anticancer activity. We studied the effects of ART on proliferation and apoptosis of human K562 and U937 leukemia cell lines. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay demonstrated that ART inhibits cell growth in a dose- and time-dependent manner. Based on the findings obtained from light, fluorescence and transmission electron microscopy and propidium iodide staining, the effect of ART was shown to be mediated through apoptosis. In parallel, ART treatment increased Fas expression, while it decreased the c-Fos level in K562 cells. Furthermore, co-treatment with arsenic trioxide (ATO) significantly facilitated ART-induced K562 cell apoptosis. These findings demonstrated that ART had an antitumor activity against K562 and U937 leukemia cells, largely due to inhibition of proliferation and induction of apoptosis via the intrinsic pathway; and this tumoricidal function could be enhanced by ATO.

Keywords::

• Artesunate
• anti-leukemia
• arsenic trioxide

Acknowledgements

This work was supported by grants from the Natural Science Foundation of Shandong Province, China (Nos. Y2007C053; ZR2009CM059) and the Project of Scientific and Technological Development of Shandong Province, China (No. 2007GG10002008; 2008GG2NS02018; 2010GSF10250).

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