Negative regulation of β-catenin/Tcf signaling by naringenin in AGS gastric cancer cell

被引:43
作者
Lee, JH [1 ]
Park, CH [1 ]
Jung, KC [1 ]
Rhee, HS [1 ]
Yang, CH [1 ]
机构
[1] Seoul Natl Univ, Div Chem & Mol Engn, Seoul 151742, South Korea
关键词
beta-catenin/Tcf signaling; naringenin; nuclear beta-catenin; mechanism;
D O I
10.1016/j.bbrc.2005.07.146
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Functional activation of beta-catenin/Tcf signaling plays an important role in early events in carcinogenesis. We examined the effect of naringenin against beta-catenin/Tcf signaling in gastric cancer cells. Reporter gene assay showed that naringenin inhibited beta-catenin/Tcf signaling efficiently. In addition, the inhibition of beta-catenin/Tcf signaling by naringenin in HEK293 cells transiently transfected with constitutively mutant beta-catenin gene, whose product is not phosphorylated by GSK3 beta, indicates that its inhibitory mechanism was related to beta-catenin itself or downstream components. To investigate the precise inhibitory mechanism, we performed immunofluorescence, Western blot, and EMSA. As a result, our data revealed that the beta-catcnin distribution and the levels of nuclear beta-catenin and Tcf-4 proteins were unchanged after naringenin treatment. Moreover, the binding activities of Tcf complexes to consensus DNA were not affected by naringenin. Taken together, these data suggest that naringenin inhibits beta-catenin/Tcf signaling in gastric cancer with unknown mechanisms. (C) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:771 / 776
页数:6
相关论文
共 33 条
[1]  
Caca K, 1999, CELL GROWTH DIFFER, V10, P369
[2]  
Clements WM, 2002, CANCER RES, V62, P3503
[3]   The metalloproteinase matrilysin is a target of β-catenin transactivation in intestinal tumors [J].
Crawford, HC ;
Fingleton, BM ;
Rudolph-Owen, LA ;
Goss, KJH ;
Rubinfeld, B ;
Polakis, P ;
Matrisian, LM .
ONCOGENE, 1999, 18 (18) :2883-2891
[4]   Tyrosine phosphorylation and cadherin/catenin function [J].
Daniel, JM ;
Reynolds, AB .
BIOESSAYS, 1997, 19 (10) :883-891
[5]   Inhibition of β-catenin/Tcf activity by white tea, green tea, and epigallocatechin-3-gallate (EGCG):: minor contribution of H2O2 at physiologically relevant EGCG concentrations [J].
Dashwood, WM ;
Orner, GA ;
Dashwood, RH .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 296 (03) :584-588
[6]   The nonsteroidal anti-inflammatory drugs aspirin and indomethacin attenuate β-catenin/TCF-4 signaling [J].
Dihlmann, S ;
Siermann, A ;
Doeberitz, MV .
ONCOGENE, 2001, 20 (05) :645-653
[7]   MODULATING EFFECT OF PLANT FLAVONOIDS ON THE MUTAGENICITY OF N-METHYL-N'-NITRO-N-NITROSOGUANIDINE [J].
FRANCIS, AR ;
SHETTY, TK ;
BHATTACHARYA, RK .
CARCINOGENESIS, 1989, 10 (10) :1953-1955
[8]   Frequent β-catenin aberration in human hepatocellular carcinoma [J].
Fujie, H ;
Moriya, K ;
Shintani, Y ;
Tsutsumi, T ;
Takayama, T ;
Makuuchi, M ;
Kimura, S ;
Koike, K .
HEPATOLOGY RESEARCH, 2001, 20 (01) :39-51
[9]   Anti-Helicobacter pylori flavonoids from licorice extract [J].
Fukai, T ;
Marumo, A ;
Kaitou, K ;
Kanda, T ;
Terada, S ;
Nomura, T .
LIFE SCIENCES, 2002, 71 (12) :1449-1463
[10]   Identification of c-MYC as a target of the APC pathway [J].
He, TC ;
Sparks, AB ;
Rago, C ;
Hermeking, H ;
Zawel, L ;
da Costa, LT ;
Morin, PJ ;
Vogelstein, B ;
Kinzler, KW .
SCIENCE, 1998, 281 (5382) :1509-1512