Paeonia lactiflora Pall inhibits bladder cancer growth involving phosphorylation of Chk2 in vitro and in vivo

被引:64
作者
Ou, Ting-Tsz [1 ]
Wu, Cheng-Hsun [2 ]
Hsu, Jeng-Dong [3 ]
Chyau, Charng-Cherng [4 ]
Lee, Huei-Jane [1 ]
Wang, Chau-Jong [1 ,5 ]
机构
[1] Chung Shan Med Univ, Inst Biochem & Biotechnol, Coll Med, Taichung 402, Taiwan
[2] China Med Univ, Dept Anat, Taichung, Taiwan
[3] Chung Shan Med Univ Hosp, Dept Pathol, Taichung, Taiwan
[4] Hung Kuang Univ, Coll Med & Nursing, Inst Biotechnol, Taichung, Taiwan
[5] Chung Shan Med Univ Hosp, Dept Med Res, Taichung, Taiwan
关键词
Paeonia lactiflora Pall (RPA); Apoptosis; Cell cycle; G2/M phase; Checkpoint kinase 2; Bladder carcinogenesis; CELL-CYCLE ARREST; URINARY-BLADDER; IMMUNOLOGICAL ACTIVITIES; ACIDIC POLYSACCHARIDE; PEONIA-LACTIFLORA; TEA POLYPHENOLS; CARCINOMA-CELLS; ACTIVATION; APOPTOSIS; CHECKPOINTS;
D O I
10.1016/j.jep.2011.03.011
中图分类号
Q94 [植物学];
学科分类号
071001 [植物学];
摘要
Ethnopharmacological relevance: Extracts of Paeonia lactiflora Pall (RPA), a traditional Chinese medicines has been shown to treat cancers. Aim of the study: The purpose of this study is to evaluate the anticancer effect of RPA in urinary bladder carcinoma in vitro and in vivo. Materials and methods: The cell viability was analyzed with DAPI. Flow cytometry and Western blot were used to study the apoptosis and cell cycle related mechanism. A rat model of bladder cancer was induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBN). Tumors were analyzed with immunohistochemical analysis. Results: Our data suggested that RPA inhibits growth of bladder cancer via induction of apoptosis and cell cycle arrest. Treatment of TSGH-8301 cells with RPA resulted in G2-M phase arrest that was associated with a marked decline in protein levels of cdc2, cyclin B1, cell division cycle 25B (Cdc25B) and Cdc25 C. We also reported that RPA-mediated growth inhibition of TSGH-8301 cells was correlated with activation of checkpoint kinase 2 (Chk2). Herein, we further evaluated urinary bladder cancer using a model of bladder cancer induced by OH-BBN. Analysis of tumors from RPA-treated rats showed significant decrease in the expression of Bcl2, cyclin D1, and PCNA, and increase in the expression of p-Chk2 (Thr-68). Bax, and Cip1/p21. Conclusion: Our data provide the experimental evidence that RPA could modulate apoptosis in models of bladder cancer. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:162 / 172
页数:11
相关论文
共 44 条
[1]
The Bcl-2 protein family: Arbiters of cell survival [J].
Adams, JM ;
Cory, S .
SCIENCE, 1998, 281 (5381) :1322-1326
[2]
Phosphorylation of threonine 68 promotes oligomerization and autophosphorylation of the Chk2 protein kinase via the forkhead-associated domain [J].
Ahn, JY ;
Li, XH ;
Davis, HL ;
Canman, CE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (22) :19389-19395
[3]
Ahn JY, 2000, CANCER RES, V60, P5934
[4]
Mammalian G1- and S-phase checkpoints in response to DNA damage [J].
Bartek, J ;
Lukas, J .
CURRENT OPINION IN CELL BIOLOGY, 2001, 13 (06) :738-747
[5]
QUERCETIN AND RUTIN AS INHIBITORS OF AZOXYMETHANOL-INDUCED COLONIC NEOPLASIA [J].
DESCHNER, EE ;
RUPERTO, J ;
WONG, G ;
NEWMARK, HL .
CARCINOGENESIS, 1991, 12 (07) :1193-1196
[6]
Mutations in CHEK2 associated with prostate cancer risk [J].
Dong, XY ;
Wang, L ;
Taniguchi, K ;
Wang, XS ;
Cunningham, JM ;
McDonnell, SK ;
Qian, CP ;
Marks, AF ;
Slager, SL ;
Peterson, BJ ;
Smith, BI ;
Cheville, JC ;
Blute, ML ;
Jacobsen, SJ ;
Schaid, DJ ;
Tindall, DJ ;
Thibodeau, SN ;
Liu, WG .
AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 72 (02) :270-280
[7]
Mammalian caspases: Structure, activation, substrates, and functions during apoptosis [J].
Earnshaw, WC ;
Martins, LM ;
Kaufmann, SH .
ANNUAL REVIEW OF BIOCHEMISTRY, 1999, 68 :383-424
[8]
The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis [J].
Falck, J ;
Mailand, N ;
Syljuåsen, RG ;
Bartek, J ;
Lukas, J .
NATURE, 2001, 410 (6830) :842-847
[9]
CHECKPOINTS - CONTROLS THAT ENSURE THE ORDER OF CELL-CYCLE EVENTS [J].
HARTWELL, LH ;
WEINERT, TA .
SCIENCE, 1989, 246 (4930) :629-634
[10]
CELL-CYCLE CONTROL AND CANCER [J].
HARTWELL, LH ;
KASTAN, MB .
SCIENCE, 1994, 266 (5192) :1821-1828