Proanthocyanidin from grape seeds inactivates the PI3-kinase/PKB pathway and induces apoptosis in a colon cancer cell line

被引:131
作者
Engelbrecht, A. -M. [1 ]
Mattheyse, M. [1 ]
Ellis, B. [1 ]
Loos, B. [1 ]
Thomas, M. [1 ]
Smith, R. [1 ]
Peters, S. [1 ]
Smith, C. [1 ]
Myburgh, K. [1 ]
机构
[1] Univ Stellenbosch, Dept Physiol Sci, ZA-7600 Stellenbosch, South Africa
关键词
PI3-k; PKB/Akt; apoptosis; colon cancer;
D O I
10.1016/j.canlet.2007.08.020
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The aim of this investigation was to evaluate the chemopreventative/antiproliferative potential of a grape seed proanthocyanidin extract (GSPE) against colon cancer cells (CaCo2 cells) and to investigate its mechanism of action. GSPE (10-100 mu g/ml) significantly inhibited cell viability and increased apoptosis in CaCo2 cells, but did not alter viability in the normal colon cell line (NCM460). The increased apoptosis observed in GSPE-treated CaCo2 cells correlated with an attenuation of PI3-kinase (p 110 and p85 subunits) and decreased PKB Ser 473 phosphorylation. GSPE might thus exert its beneficial effects by means of increased apoptosis and suppression of the important PI3-kinase survival-related pathway. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:144 / 153
页数:10
相关论文
共 42 条
[1]   Grape seed extract induces apoptotic death of human prostate carcinoma DU145 cells via caspases activation accompanied by dissipation of mitochondrial membrane potential and cytochrome c release [J].
Agarwal, C ;
Singh, RP ;
Agarwal, R .
CARCINOGENESIS, 2002, 23 (11) :1869-1876
[2]   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
[3]   Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention [J].
Bagchi, D ;
Bagchi, M ;
Stohs, SJ ;
Das, DK ;
Ray, SD ;
Kuszynski, CA ;
Joshi, SS ;
Pruess, HG .
TOXICOLOGY, 2000, 148 (2-3) :187-197
[4]   Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1 [J].
Biggs, WH ;
Meisenhelder, J ;
Hunter, T ;
Cavenee, WK ;
Arden, KC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (13) :7421-7426
[5]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[6]   Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor [J].
Brunet, A ;
Bonni, A ;
Zigmond, MJ ;
Lin, MZ ;
Juo, P ;
Hu, LS ;
Anderson, MJ ;
Arden, KC ;
Blenis, J ;
Greenberg, ME .
CELL, 1999, 96 (06) :857-868
[7]   Involvement of the pathway phosphatidylinositol-3-kinase/AKT-1 in the establishment of the survival response to ionizing radiation [J].
Cataldi, A ;
Zauli, G ;
Di Pietro, Z ;
Castorina, S ;
Rana, R .
CELLULAR SIGNALLING, 2001, 13 (05) :369-375
[8]  
Fang Q, 2006, ANTICANCER RES, V26, P203
[9]   Characterization of proanthocyanidins from grape seeds [J].
Gabetta, B ;
Fuzzati, N ;
Griffini, A ;
Lolla, E ;
Pace, R ;
Ruffilli, T ;
Peterlongo, F .
FITOTERAPIA, 2000, 71 (02) :162-175
[10]   Use of the MTT assay in adult ventricular cardiomyocytes to assess viability: Effects of adenosine and potassium on cellular survival [J].
Gomez, LA ;
Alekseev, AE ;
Aleksandrova, LA ;
Brady, PA ;
Terzic, A .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1997, 29 (04) :1255-1266