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A novel organoselenium compound induces cell cycle arrest and apoptosis in prostate cancer cell lines
Shi, CJ; Yu, LZ; Yang, FG; Yan, J; Zeng, HH
关键词prostate cancer cell cycle apoptosis Cyclins cdks cell block organoselenium compound anticancer agent
刊名BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
2003-09-26
DOI10.1016/j.bbrc.2003.08.032
309期:3页:578-583
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]HUMAN THIOREDOXIN ; HUMAN TUMORS ; GROWTH ; EXPRESSION ; INHIBITOR ; DISULFIDE ; LEUKEMIA ; KINASES ; P21
英文摘要

Thioredoxin reductase (TrxR) in conjunction with thioredoxin (Trx) is a ubiquitous intracellular oxidoreductase system with antioxidant and redox regulatory roles. The properties of TrxR in combination with the functions of Trx position this system at the core of cellular thiol redox control and antioxidant defense. In some human tumors, the thioredoxin system is found overexpressed. Because of its role in stimulating cancer cell growth and as an inhibitor of apoptosis, the Trx system offers a target for the development of drugs to treat and prevent cancer. In a previous research, we successfully synthesized a novel organoselenium compound BBSKE(1,2-[bis(1,2-Benzisoselenazolone-3(2H)-ketone)]ethane, BBSKE, PCT: CN02/00412) targeting the TrxR, and it has demonstrated the inhibitory effect on the growth of a variety of human cancer cells from various organs. In this study, we investigated the inhibitory effect of BBSKE on TrxR activity in PC-3 and DU145 human prostate cancer cell lines, and its antitumoral effect on these two cell lines. Treatment of BBSKE inhibited the TrxR activity in both of the cell lines in a dose-dependent manner and it also inhibited the proliferation of these two cell lines in a dose-dependent manner. Cell cycle analysis showed S phase arrest in both of the cell lines following 48 h exposure to BBSKE. During the S arrest, analysis of cell cycle regulatory proteins demonstrated that BBSKE increased the protein levels of cyclinA, cyclinE, and P21, but decreased the levels of cyclinB1, cyclinD1, and Cdk4. Furthermore, BBSKE decreased the protein level of Bcl-2 but increased the level of Bax, and induced apoptosis in PC-3 and DU145 human prostate cancer cell lines. These results suggest that this novel TrxR inhibitor inhibits the proliferation of prostate cancer cells via S phase arrest and apoptosis in association with the regulation of multiple molecules in the cell cycle. (C) 2003 Elsevier Inc. All rights reserved.

语种英语
WOS记录号WOS:000185353600014
引用统计
被引频次:60[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64726
专题北京大学药学院_化学生物学系
作者单位1.Peking Univ, Sch Pharmaceut Sci, Dept Biochem, Beijing 100083, Peoples R China
2.Peking Univ, Hosp 1, Inst Urol, Dept Mol Biol, Beijing 100034, Peoples R China
推荐引用方式
GB/T 7714
Shi, CJ,Yu, LZ,Yang, FG,et al. A novel organoselenium compound induces cell cycle arrest and apoptosis in prostate cancer cell lines[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2003,309(3):578-583.
APA Shi, CJ,Yu, LZ,Yang, FG,Yan, J,&Zeng, HH.(2003).A novel organoselenium compound induces cell cycle arrest and apoptosis in prostate cancer cell lines.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,309(3),578-583.
MLA Shi, CJ,et al."A novel organoselenium compound induces cell cycle arrest and apoptosis in prostate cancer cell lines".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 309.3(2003):578-583.
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