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


CONCLUSIONS
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.
School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
Lin
L
Deng
School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
Rui
R
Zhang
School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
Feng
F
Tang
School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
Chen
C
Li
School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
Ying-Ying
YY
Xing
School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: xi_tao18@yahoo.com.cn.
Tao
T
Xi
D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D007938:Leukemia / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*; D020298:U937 Cells; D000097245:Ursolic Acid
D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D014315:Triterpenes; D000097245:Ursolic Acid
Differentiation; PI3K/Akt; Phosphorylation; R285; U937; Ursolic acid (UA)