Triptolide inhibits colon-rectal cancer cells proliferation by induction of G1 phase arrest through upregulation of p21

被引:53
作者
Liu, Juanjuan [1 ]
Shen, Min [2 ]
Yue, Zhenggang [1 ]
Yang, Zhifu [3 ]
Wang, Meng [1 ]
Li, Chen [1 ]
Xin, Chunyan [1 ]
Wang, Yukun [1 ]
Mei, Qibing [1 ]
Wang, Zhipeng [1 ]
机构
[1] Fourth Mil Med Univ, Key Lab Gastrointestinal Pharmacol Chinese Mat Me, State Adm Tradit Chinese Med, Dept Pharmacol,Sch Pharm, Xian 710032, Peoples R China
[2] Fourth Mil Med Univ, Dept Cardiovasc Dis, Xijing Hosp, Xian 710032, Peoples R China
[3] Fourth Mil Med Univ, Dept Pharmaceut, Tangdu Hosp, Xian 710032, Peoples R China
基金
中国国家自然科学基金;
关键词
Cell cycle; Colon-rectal cancer; Triptolide; Tripterygium wilfordii; p21; PROTEIN-KINASE; CYCLIN-A; ACTIVATION; EXPRESSION; APOPTOSIS; PATHWAY; LINES; GENE; AKT; MEK;
D O I
10.1016/j.phymed.2012.02.014
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Triptolide, a diterpene triepoxide compound extracted from the traditional Chinese medicine herb Tripterygium wilfordii Hook F., is a potential cancer chemotherapeutic for tumors. However, the mechanism of anti-proliferative mechanism of triptolide in colon cancer cells is not entirely clear. Triptolide markedly inhibited HT29 and SW480 cells proliferation in a dose- and time-dependent manner. Triptolide decreased ERR and ART phosphorylation, and GABP alpha expression in colon cancer cells. Beta-catenin expression and phosphorylation were not altered by incubation of triptolide. However, we found that triptolide repressed expression of LEF/TCF. Although it did not significantly affect cells apoptosis, triptolide induced G1 phase arrest dose-dependently. Further detection for the expression of cell cycle-related proteins suggesting that triptolide stimulate expression of p21 and repress cyclin Al. Increased p21 binded to CDK4/CDK6, therefore blocked function of CDK4/CDK6, and subsequently contribute to the G1 arrest. These data suggested that triptolide is a potential agent for treatment of colon cancer, and its anti-proliferation effect mainly occur through G1 phase arrest. (C) 2012 Elsevier GmbH. All rights reserved.
引用
收藏
页码:756 / 762
页数:7
相关论文
共 24 条
[1]   Mechanism of activation of protein kinase B by insulin and IGF-1 [J].
Alessi, DR ;
Andjelkovic, M ;
Caudwell, B ;
Cron, P ;
Morrice, N ;
Cohen, P ;
Hemmings, BA .
EMBO JOURNAL, 1996, 15 (23) :6541-6551
[2]   REQUIREMENT FOR INTEGRATION OF SIGNALS FROM 2 DISTINCT PHOSPHORYLATION PATHWAYS FOR ACTIVATION OF MAP KINASE [J].
ANDERSON, NG ;
MALLER, JL ;
TONKS, NK ;
STURGILL, TW .
NATURE, 1990, 343 (6259) :651-653
[3]   Linking colorectal cancer to Wnt signaling [J].
Bienz, M ;
Clevers, H .
CELL, 2000, 103 (02) :311-320
[4]  
Chan EWC, 2001, TOXICOL LETT, V122, P81
[5]   Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb Tripterygium Wilfordii Hook F [J].
Chen, BJ .
LEUKEMIA & LYMPHOMA, 2001, 42 (03) :253-265
[6]  
COFFER P, 1994, ONCOGENE, V9, P911
[7]   New roles for p21 and p27 cell-cycle inhibitors: a function for each cell compartment? [J].
Coqueret, O .
TRENDS IN CELL BIOLOGY, 2003, 13 (02) :65-70
[8]   THE PRIMARY STRUCTURE OF MEK, A PROTEIN-KINASE THAT PHOSPHORYLATES THE ERK GENE-PRODUCT [J].
CREWS, CM ;
ALESSANDRINI, A ;
ERIKSON, RL .
SCIENCE, 1992, 258 (5081) :478-480
[9]  
DING GS, 1987, CLIN THER, V9, P345
[10]   THE PROTEIN-KINASE ENCODED BY THE AKT PROTOONCOGENE IS A TARGET OF THE PDGF-ACTIVATED PHOSPHATIDYLINOSITOL 3-KINASE [J].
FRANKE, TF ;
YANG, SI ;
CHAN, TO ;
DATTA, K ;
KAZLAUSKAS, A ;
MORRISON, DK ;
KAPLAN, DR ;
TSICHLIS, PN .
CELL, 1995, 81 (05) :727-736