School of Life Science and Technology, China Pharmaceutical University, Tong Jiaxiang, Nanjing, People's Republic of China.
Anticancer Drugs. 2011 Feb;22(2):158-65. doi: 10.1097/CAD.0b013e3283409673.
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.
熊果酸（UA）是一种五环三萜类化合物，广泛分布于植物界，具有广泛的生物学效应。本研究首次探讨了 UA 在人白血病 HL60 细胞分化中的潜在作用及其作用机制。UA 可诱导 HL60 细胞向单核细胞系分化，其形态学变化、硝基四氮唑蓝还原试验和 CD14、CD11b 表面抗原的表达均证实了这一点。此外，UA 还能以剂量和时间依赖的方式激活细胞外信号调节激酶（ERK）通路。用 PD98059 抑制 ERK 通路的激活可显著阻断 UA 诱导的分化。与诱导分化一致，UA 上调 CCAAT/增强子结合蛋白β的作用也被 PD98059 消除。综上所述，本研究结果表明，UA 通过激活 ERK 通路可促进 HL60 细胞向单核细胞分化，并增加 CCAAT/增强子结合蛋白β的表达，提示 UA 可能是一种有潜力的分化诱导剂，可用于白血病的治疗。
