Ursolic acid induces HL60 monocytic differentiation and upregulates C/EBPβ expression by ERK pathway activation.
Ursolic acid (UA), a pentacyclic triterpenoid compound, is widely distributed in the plant kingdom and has a broad range of biological effects. This study was carried out for the first time to investigate the potential role of UA in the differentiation of human leukemia HL60 cells and the underlying mechanisms in it. UA could induce differentiation of HL60 cells into the monocytic lineage, as assessed by the morphological change, nitroblue tetrazolium reduction assay, and expression of CD14 and CD11b surface antigens. Moreover, UA activated the extracellular signal-regulated kinase (ERK) pathway in both dose-dependent and time-dependent manners. Inhibiting ERK pathway activation with PD98059 could significantly block the differentiation induced by UA. Consistent with the induced differentiation, the upregulation of CCAAT/enhancer-binding protein β by UA was also eliminated by PD98059. Taken together, the results reported here show that UA can promote the monocytic differentiation of HL60 cells and increase the expression of CCAAT/enhancer-binding protein β by activating the ERK pathway, suggesting that UA could be a potential candidate as a differentiation-inducing agent for the therapeutic treatment of leukemia.
School of Life Science and Technology, China Pharmaceutical University, Tong Jiaxiang, Nanjing, People's Republic of China.
Ting
T
Zhang
Yun-Mian
YM
He
Jin-Song
JS
Wang
Jing
J
Shen
Ying-Ying
YY
Xing
Tao
T
Xi
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D045325:HCT116 Cells; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D014315:Triterpenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects; D000097245:Ursolic Acid
D000972:Antineoplastic Agents, Phytogenic; D022782:CCAAT-Enhancer-Binding Protein-beta; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D016271:Proto-Oncogene Proteins c-myc; D014315:Triterpenes; D000097245:Ursolic Acid; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one