Ursolic acid induces U937 cells differentiation by PI3K/Akt pathway activation

AIM:Ursolic acid(UA),a pentacyclic triterpenoid,is used as an anti-inflammatory and anti-cancer agent.There were few studies on the effects of UA on differentiation,and this is the first time to elucidate the potential effect and molecular mechanism of UA on inducing differentiation in the human leukemia cell line U937.METHODS:Wright-Giemsa staining,nitroblue tetrazolium reduction assay and flow cytometric analysis were utilized to demonstrate the differentiation of U937 cells induced by UA.Western blotting and immunofluorescence assay were used to investigate the possible mechanism.RESULTS:It was found that UA could induce the differentiation of U937cells and Akt-activity was significantly increased during differentiation.Additionally,LY294002,a PI3K-Akt inhibitor,could block the differentiation of U937 cells induced by UA.CONCLUSION:UA could induce the differentiation of U937 cells by activating the PI3K/Akt pathway,and it could be a potential candidate as a differentiation-inducing agent for the therapy of leukemia.