Bufalin induces G0/G1 phase arrest through inhibiting the levels of cyclin D, cyclin E, CDK2 and CDK4, and triggers apoptosis via mitochondrial signaling pathway in T24 human bladder cancer cells

被引：92

作者：

Huang, Wen-Wen ^{[1
]}

Yang, Jai-Sing ^{[2
]}

Pai, Shu-Jen ^{[1
]}

Wu, Ping-Ping ^{[3
]}

Chang, Shu-Jen ^{[3
]}

Chueh, Fu-Shin ^{[4
]}

Fan, Ming-Jen ^{[5
]}

Chiou, Shang-Ming ^{[6
,7
,8
]}

Kuo, Hsiu-Maan ^{[9
]}

Yeh, Chin-Chung ^{[10
]}

Chen, Po-Yuan ^{[1
]}

Tsuzuki, Minoru ^{[11
,12
]}

Chung, Jing-Gung ^{[1
,5
]}

机构：

[1] China Med Univ, Dept Biol Sci & Technol, Taichung 404, Taiwan

[2] China Med Univ, Dept Pharmacol, Taichung 404, Taiwan

[3] China Med Univ, Sch Pharm, Taichung 404, Taiwan

[4] Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung 413, Taiwan

[5] Asia Univ, Dept Biotechnol, Taichung 413, Taiwan

[6] China Med Univ Hosp, Dept Funct Neurosurg, Taichung 404, Taiwan

[7] China Med Univ Hosp, Gamma Knife Ctr, Taichung 404, Taiwan

[8] China Med Univ, Sch Med, Taichung 404, Taiwan

[9] China Med Univ, Dept Parasitol, Taichung 404, Taiwan

[10] China Med Univ Hosp, Dept Urol, Taichung 404, Taiwan

[11] Nihon Pharmaceut Univ, Dept Biochem, Ina, Saitama 3620806, Japan

[12] China Med Univ, Tsuzuki Inst Tradit Med, Taichung 404, Taiwan

来源：

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS | 2012年 / 732卷 / 1-2期

关键词：

Bufalin; T24 human bladder cancer cells; G(0)/G(1) phase arrest; Apoptosis; Mitochondrial signaling pathway; HUMAN LEUKEMIA-CELLS; PROTEIN-KINASE; DEPENDENT PATHWAYS; MOLECULAR-CLONING; LUNG-CANCER; U937; CELLS; IN-VITRO; PHOSPHORYLATION; NECROSIS; BAX;

D O I：

10.1016/j.mrfmmm.2011.09.010

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

Most of the chemotherapy treatments for bladder cancer aim to kill the cancer cells, but a high recurrence rate after medical treatments is still occurred. Bufalin from the skin and parotid venom glands of toad has been shown to induce apoptotic cell death in many types of cancer cell lines. However, there is no report addressing that bufalin induced cell death in human bladder cancer cells. The purpose of this study was investigated the mechanisms of bufalin-induced apoptosis in a human bladder cancer cell line (T24). We demonstrated the effects of bufalin on the cell growth and apoptosis in T24 cells by using DAPI/TUNEL double staining, a PI exclusion and flow cytometric analysis. The effects of bufalin on the production of reactive oxygen species (ROS), the level of mitochondrial membrane potential (Delta Psi(m)), and DNA content including sub-G1 (apoptosis) in T24 cells were also determined by flow cytometry. Western blot analysis was used to examine the expression of G(0)/G(1) phase-regulated and apoptosis-associated protein levels in bufalin-treated T24 cells. The results indicated that bufalin significantly decreased the percentage of viability, induced the G(0)/G(1) phase arrest and triggered apoptosis in T24 cells. The downregulation of the protein levels for cyclin D, CDK4, cyclin E, CDK2, phospho-Rb, phospho-AKT and Bcl-2 with the simultaneous up-regulation of the cytochrome c, Apaf-1, AIF, caspase-3, -7 and -9 and Sax protein expressions and caspase activities were observed in T24 cells after bufalin treatment. Based on our results, bufalin induces apoptotic cell death in T24 cells through suppressing AKT activity and antiapoptotic Bcl-2 protein as well as inducing pro-apoptotic Bax protein. The levels of caspase-3, -7 and -9 are also mediated apoptosis in bufalin-treated T24 cells. Therefore, bufalin might be used as a therapeutic agent for the treatment of human bladder cancer in the future. (C) 2012 Elsevier B.V. All rights reserved.

引用

页码：26 / 33

页数：8

共 39 条

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