Ursolic Acid-induced Apoptosis in K562 Cells Involving Upregulation of PTEN Gene Expression and Inactivation of the PI3K/Akt Pathway

被引:50
作者
Wu, Bin [1 ]
Wang, Xu [2 ]
Chi, Zuo-fei [1 ]
Hu, Rong [1 ]
Zhang, Rong [1 ]
Yang, Wei [1 ]
Liu, Zhuo-gang [1 ]
机构
[1] China Med Univ, Shengjing Hosp, Dept Hematol, Shenyang, Peoples R China
[2] China Med Univ, Hosp 1, Endoscopy Ctr, Shenyang, Peoples R China
关键词
Ursolic acid; PTEN; K562; Apoptosis; MYELOID-LEUKEMIA CELLS; SIGNALING PATHWAY; CANCER CELLS; ACTIVATION; SURVIVAL; DEPHOSPHORYLATES; INDUCTION; KINASE;
D O I
10.1007/s12272-012-0318-1
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Ursolic acid (UA), a pentacyclic triterpenoid derived from a variety of medicinal plants, exhibits potent anticancer activity against many types of cancer cells. However, the anticancer mechanism of UA is not clearly understood. Suppression of phosphatase and a tensin homolog deleted on chromosome 10 (PTEN) gene expression leading to activation of the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway has been observed in many cancers including leukemia, making the PTEN gene and PI3K/Akt pathway a central target for cancer therapy. Here, we demonstrated that UA was able to inhibit growth, induce apoptosis in a human chronic myelogenous leukemia cell line (K562 cells) via upregulation of PTEN gene expression, inhibit Akt kinase activity, change mitochondrial transmembrane potential and reduce the release of cytochrome c and the activity of caspases. These results suggest that UA may elicit its strong antitumor effects via upregulation of the PTEN gene and inhibition of the PI3K/Akt pathway.
引用
收藏
页码:543 / 548
页数:6
相关论文
共 21 条
[1]   The Akt/PKB pathway: molecular target for cancer drug discovery [J].
Cheng, JQ ;
Lindsley, CW ;
Cheng, GZ ;
Yang, H ;
Nicosia, SV .
ONCOGENE, 2005, 24 (50) :7482-7492
[2]   Caspases: the executioners of apoptosis [J].
Cohen, GM .
BIOCHEMICAL JOURNAL, 1997, 326 :1-16
[3]  
Gayathri R, 2009, ASIAN PAC J CANCER P, V10, P933
[4]   PI3-kinase/Akt is constitutively active in primary acute myeloid leukaemia cells and regulates survival and chemoresistance via NF-κB, MAPkinase and p53 pathways [J].
Grandage, VL ;
Gale, RE ;
Linch, DC ;
Khwaja, A .
LEUKEMIA, 2005, 19 (04) :586-594
[5]   TRAIL-induced apoptosis proceeding from caspase-3-dependent and -independent pathways in distinct HeLa cells [J].
Lin, Juqiang ;
Zhang, Zhihong ;
Zeng, Shaoqun ;
Zhou, Shixia ;
Liu, Bi-Feng ;
Liu, Qian ;
Yang, Jie ;
Luo, Qingming .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 346 (04) :1136-1141
[6]   Early phase of amyloid β42-induced cytotoxicity in neuronal cells is associated with vacuole formation and enhancement of exocytosis [J].
Liu, ML ;
Hong, ST .
EXPERIMENTAL AND MOLECULAR MEDICINE, 2005, 37 (06) :559-566
[7]   Induction of apoptosis and regulation of the MAPK pathway by ursolic acid in human leukemia K562 cells [J].
Liu, Xiao-Shan ;
Jiang, Jikai .
PLANTA MEDICA, 2007, 73 (11) :1192-1194
[8]   The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate [J].
Maehama, T ;
Dixon, JE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (22) :13375-13378
[9]   Colorectal cancer - Mutations in a signalling pathway [J].
Parsons, DW ;
Wang, TL ;
Samuels, Y ;
Bardelli, A ;
Cummins, JM ;
DeLong, L ;
Silliman, N ;
Ptak, J ;
Szabo, S ;
Willson, JKV ;
Markowitz, S ;
Kinzler, K ;
Vogelstein, B ;
Lengauer, C ;
Velculescu, VE .
NATURE, 2005, 436 (7052) :792-792
[10]   Insulinlike growth factor-I signaling in multiple myeloma: downstream elements, functional correlates, and pathway cross-talk [J].
Qiang, YW ;
Kopantzev, E ;
Rudikoff, S .
BLOOD, 2002, 99 (11) :4138-4146