Artesunate,a Antimalarial Agent,Exhibits Potent Anti-Leukemia Activities in Vitro and Inbibit Wnt/b-Catenin Pathway.

Abstract 4822

Artesunate (ART), a remarkable antimalarial agent, its antitumor effect was widely studied recently. But whether the antitumor mechanisms of ART involves in Wnt/b-catenin signalling, a major oncogenic pathway have yet been poorly understood. In address this question,we treated human leukemia cell lines,such as K562 cells, HL-60 cells,U937cells and KG1a cells with 12.5ug/ml,50ug/ml, 100 ug/ml and 200ug/ml ART for 24h, 48h and 72h respectively. Determined by the Cell Counting Kit-8 and flow cytometry analysis on apoptosis, we found that ART suppressed the leukemia cells proliferation and promoted the apoptosis of leukemia cells in a time- and concentration-dependent manner. Furthermore, we detected the mRNA level and protein expression of b-catenin and Wnt/b-catenin target genes c-myc and cyclinD1 by QRT-PCR and western blotting when the above leukemia cell lines treated with ART for 48h. The results demonstrated that the the mRNA level and protein expression of c-myc and cyclinD1 was lower in ART groups than in the contorl groups,and in concentration-dependent manner. on the other hand, there was no significant difference in the mRNA level and protein expression of b-catenin in the ART groups compare to the contorl groups. Moreover, we observed b-catenin by immunofluorescence technology, the Bioluminescent imaging demonstrated that ART translocated b-catenin from nucleus to adherent junctions of membrane,and binding to E-cadherin on the cell membrane. Our results provide the vitro evidence for the anti-luekemia mechanism of ART correlated to the inhibition of hyperactive Wnt/b-catenin signaling pathway. Combination With the present studies, the antitumor mechanism of ART is invoved in multiple signaling pathways, and the well known low toxicity. We thus speculate that ART might be a promising candidate drug for the treatment of leukemia.