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Ursolic acid induces HL60 monocytic differentiation and upregulates C/EBPβ expression by ERK pathway activation.

Abstract
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.
AuthorsTing Zhang, Yun-Mian He, Jin-Song Wang, Jing Shen, Ying-Ying Xing, Tao Xi
JournalAnti-cancer drugs (Anticancer Drugs) Vol. 22 Issue 2 Pg. 158-65 (Feb 2011) ISSN: 1473-5741 [Electronic] England
PMID20948428 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents, Phytogenic
  • CCAAT-Enhancer-Binding Protein-beta
  • Flavonoids
  • Proto-Oncogene Proteins c-myc
  • Triterpenes
  • Extracellular Signal-Regulated MAP Kinases
  • ursolic acid
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
Topics
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • CCAAT-Enhancer-Binding Protein-beta (biosynthesis, genetics, metabolism)
  • Cell Differentiation (drug effects)
  • Cell Growth Processes (drug effects)
  • Cell Line, Tumor
  • Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
  • Flavonoids (pharmacology)
  • HCT116 Cells
  • HL-60 Cells
  • Humans
  • Leukemia, Myeloid, Acute (drug therapy, genetics, metabolism, pathology)
  • MAP Kinase Signaling System (drug effects)
  • Phosphorylation (drug effects)
  • Proto-Oncogene Proteins c-myc (biosynthesis, genetics)
  • Triterpenes (antagonists & inhibitors, pharmacology)
  • U937 Cells
  • Up-Regulation (drug effects)

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