Herbal Extract Ursolic Acid On Acute Myelogenous Leukemia Cell Lines And Skno Kasumi - 1-1 Of Anti-leukemia Effect And Its Mechanism

Objective: The purpose of this study is to investigate the anti-tumor effect of Ursolic Acid (UA) in t(8;2) leukemia cell lines Kasumi-1and Skno-1and its possible mechanismisms of inhibiting proliferation and inducing apoptosis.Methods:Kasumi-1and Skno-1cells were treated with UA at different concentration for different duration. The growth inhibition of UA was detected by using CCK-8test, and then the morphological changes of the two kinds of cells were observed by Wright’s staining. Furthermore, the apoptosis rates and differentiation of Kasumi-1and Skno-1were examined by flow cytometry. Also the effect of inducing apoptosis was verified by TUNEL. Lastly, the mRNA levels of mRNA which related to differentiation, apoptosis and proliferation, were detected by using real-time quantitative PCR method, and occasionally, the proteins of amll-eto, KIT, myc, ccndl, bcl2, mdm2, p53were tested by western blot. Results:UA obviously inhibited the growth of Kasumi-1and Skno-1cells in a dose and time dependent manners. As for morphological changes, characteristic apoptotic cells were presented in both of the two kinds of cells treated with UA for48hours. The apoptotic rates of Kasumi-1and Skno-1cells increased in a dose and time dependent ways by flow cytometry, and the mRNA levels of AML1-ETO, KIT, MYC, CCND1, BCL2, MDM2decreased after treatment of UA in the two kind of cells, as well as the protein levels. Occasionally, UA up-regulated the mRNA and protein levels of P53in the same manner. The expression levels of HLA-DR, CD34, CD117were decreased in Kasumi-1cells treated with UA for72hours detected by flow cytometry while the expression of CD11b was increased at the same time, but the same results were not observed in Skno-1cells. However, the expression of CEBP, PU.1, ICSBP and GM-CSF were up-regulated in both kinds of cells detected by RT-PCR. Conclusion:UA can exert its anti-tumor effect by inhibiting proliferation and inducing apoptosis of Kasumi-1and Skno-1cells in a dose-dependent and time-dependent manners. Also, the UA may have a trend of inducing differentiation to these kinds of cells. All the results above may be provide the clues of a new target therapy to t(8;21) leukemia.