The Anti-cancer Effects And Mechanism Of Artesunate

Artesunate is a important derivate of artemisinin which is an anti-malaria medicine of sesquiterpene-lactone group. As a anti-malaria medicine with new constitution, artesunate possess some features, including high performance, immediate effect, low toxicity and so on. Since 1990s, anti-cancer effects of artesunate had been discovered which brought about general interest. In this study, we researched anti-cancer activity of artesunate in vivo and in vitro, action of inducing cell apoptosis, effect of gene and protein expression about apoptosis and the interaction of artesunate with clinic anti-cancer medicine.The result of antitumor experiment in vivo suggests artesunate can significant inhibit growth of Lewis and S180 tumor. When dosage is up to 200mg/kg, percentage of antitumor is 60.91% and 57%, respectively. Through MTT assay, result shows Art can effectively inhibit tumor cells growth (including HL60 KB OV3 BGC823 HCT B16-BL6 Hela A549 A43l HepG-2 SGC7901 KCC853 and GLC-82), IC50 is from 0.4g mL-1 to 52.16g mL-1.Tumor cells were exposured to different concentrations of Art, apoptosis was examined by fluorescent staining, flow cytometry, agarose gel electrophoresis (AGE) and caspase-3 activity assay. With Art treatment, HL60 cells showed typical apoptotic features, including chromatin condensation and apoptotic bodies (fluorescent staining), and apoptosis rate of tumor cells increasing in concentration-dependent manners (flow cytometry), DNA ladder (AGE), activity of caspase-3 enhancing.Art effects expression of crucial gene and protein in passway of apoptosis, too. Art can decrease expression of Bcl-2 protein ( from 89.51% to 63.78% ) and enhance expression of Bax protein (from 45.76% to 74.96%), reduce expression of survivin mRNA and survivin protein in concentration-dependent manners. Expression of c-myc is reduced, too.Flow cytometric analysis indicates that Art can effect two checkpoints of cell cycle, G1/S and G2/M. Compared with control group, cell percentage in G1/S and G2/M stage treated with Art is significant increased, cells are inhibited in G1stage and G2/M stage.In a word, Art is of strong anticancer effect which is associated with inducing cells apoptosid and effecting cell cycle. Art combination with Cisplatin indicate better anticancer effect.