Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo

被引:220
作者
Bai, Yu [1 ]
Mao, Qi-Qi [1 ]
Qin, Jie [1 ]
Zheng, Xiang-Yi [1 ]
Wang, Yun-Bin [1 ]
Yang, Kai [1 ]
Shen, Hua-Feng [1 ]
Xie, Li-Ping [1 ]
机构
[1] Zhejiang Univ, Coll Med, Affiliated Hosp 1, Dept Urol, Hangzhou 310003, Zhejiang, Peoples R China
关键词
PI3K-AKT PATHWAY; KINASE PATHWAYS; EPIDEMIOLOGY; ANGIOGENESIS; PROGRESSION; ACTIVATION; EXPRESSION; PI3K/AKT; TARGETS; GRAPES;
D O I
10.1111/j.1349-7006.2009.01415.x
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Resveratrol, a naturally occurring polyphenolic antioxidant compound present in grapes and red wine, has been reported to hold various biochemical responses. In this preliminary study, we evaluate the chemopreventive potential of resveratrol against bladder cancer and its mechanism of action. Treatment of bladder cancer cells with resveratrol resulted in a significant decrease in cell viability. Resveratrol induced apoptosis through the modulation of Bcl-2 family proteins and activation of caspase 9 and caspase 3 followed by poly(ADP-ribose) polymerase degradation. Treatment with resveratrol led to G1 phase cell cycle arrest in T24 cells by activation of p21 and downregulation of cyclin D1, cyclin-dependent kinase 4, and phosphorylated Rb. Resveratrol also inhibited the phosphorylation of Akt, whereas the phosphorylation of p38 MAPK was enhanced. In addition, resveratrol treatment decreased the expression of vascular endothelial growth factor and fibroblast growth factor-2, which might contribute to the inhibition of tumor growth on the bladder cancer xenograft model. These findings suggest that reveratrol could be an important chemoprevention agent for bladder cancer. (Cancer Sci 2010; 101: 488-493)
引用
收藏
页码:488 / 493
页数:6
相关论文
共 33 条
[1]
Ahmad N, 2001, CLIN CANCER RES, V7, P1466
[2]
Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3′-kinase/Akt pathway and Bcl-2 family proteins [J].
Aziz, Moammir H. ;
Nihal, Minakshi ;
Fu, Vivian X. ;
Jarrard, David F. ;
Ahmad, Nihal .
MOLECULAR CANCER THERAPEUTICS, 2006, 5 (05) :1335-1341
[3]
Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance [J].
Boehm, T ;
Folkman, J ;
Browder, T ;
OReilly, MS .
NATURE, 1997, 390 (6658) :404-407
[4]
Bradamante S, 2004, CARDIOVASC DRUG REV, V22, P169
[5]
Osmotic stress regulates the stability of cyclin D1 in a p38SAPK2-dependent manner [J].
Casanovas, O ;
Miró, B ;
Estanyol, JM ;
Itarte, E ;
Agell, N ;
Bachs, O .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (45) :35091-35097
[6]
AKT/PKB and other D3 phosphoinositide-regulated kinases: Kinase activation by phosphoinositide-dependent phosphorylation [J].
Chan, TO ;
Rittenhouse, SE ;
Tsichlis, PN .
ANNUAL REVIEW OF BIOCHEMISTRY, 1999, 68 :965-1014
[7]
Clément MV, 1998, BLOOD, V92, P996
[8]
PI3K/Akt and apoptosis: size matters [J].
Franke, TF ;
Hornik, CP ;
Segev, L ;
Shostak, GA ;
Sugimoto, C .
ONCOGENE, 2003, 22 (56) :8983-8998
[9]
DEFINITION OF 2 ANGIOGENIC PATHWAYS BY DISTINCT ALPHA(V) INTEGRINS [J].
FRIEDLANDER, M ;
BROOKS, PC ;
SHAFFER, RW ;
KINCAID, CM ;
VARNER, JA ;
CHERESH, DA .
SCIENCE, 1995, 270 (5241) :1500-1502
[10]
Goldsmith Elizabeth J, 2004, Methods Mol Biol, V250, P127