中国科学院昆明植物研究所机构知识库
Advanced  
KIB OpenIR  > 植物化学与西部植物资源持续利用国家重点实验室  > 期刊论文
题名: The endoperoxide ascaridol shows strong differential cytotoxicity in nucleotide excision repair-deficient cells
作者: Abbasi, Rashda1; Efferth, Thomas2; Kuhmann, Christine1; Opatz, Till3; null(郝小江)4; Popanda, Odilia1; Schmezer, Peter1
刊名: TOXICOLOGY AND APPLIED PHARMACOLOGY
关键词: Cancer therapy ; Synthetic lethal ; Traditional Chinese medicine ; XPC ; ERCC6 ; CSB
英文摘要: Targeting synthetic lethality in DNA repair pathways has become a promising anti-cancer strategy. However little is known about such interactions with regard to the nucleotide excision repair (NER) pathway. Therefore, cell lines with a defect in the NER genes ERCC6 or XPC and their normal counterparts were screened with 53 chemically defined phytochemicals isolated from plants used in traditional Chinese medicine for differential cytotoxic effects. The screening revealed 12 drugs that killed NER-deficient cells more efficiently than proficient cells. Five drugs were further analyzed for IC50 values, effects on cell cycle distribution, and induction of DNA damage. Ascaridol was the most effective compound with a difference of >1000-fold in resistance between normal and NER-deficient cells (IC50 values for cells with deficiency in ERCC6: 0.15 mu M, XPC: 0.18 mu M, and normal cells: >180 mu M). NER-deficiency combined with ascaridol treatment led to G2/M-phase arrest, an increased percentage of subG1 cells, and a substantially higher DNA damage induction. These results were confirmed in a second set of NER-deficient and -proficient cell lines with isogenic background. Finally, ascaridol was characterized for its ability to generate oxidative DNA damage. The drug led to a dose-dependent increase in intracellular levels of reactive oxygen species at cytotoxic concentrations, but only NER-deficient cells showed a strongly induced amount of 8-oxodG sites. In summary, ascaridol is a cytotoxic and DNA-damaging compound which generates intracellular reactive oxidative intermediates and which selectively affects NER-deficient cells. This could provide a new therapeutic option to treat cancer cells with mutations in NER genes. (C) 2012 Elsevier Inc. All rights reserved.
出版日期: 2012-03-15
卷号: 259, 期号:3, 页码:302-310
DOI标识: 10.1016/j.taap.2012.01.006
语种: 英语
ISSN号: 0041-008X
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.kib.ac.cn/handle/151853/10357
Appears in Collections:植物化学与西部植物资源持续利用国家重点实验室_期刊论文

Files in This Item: Download All
File Name/ File Size Content Type Version Access License
Abbasi-2012-The endoperoxide asc.pdf(738KB)----开放获取--View Download

作者单位: 1.German Canc Res Ctr, Div Epigen & Canc Risk Factors, D-69120 Heidelberg, Germany
2.Johannes Gutenberg Univ Mainz, Inst Pharm & Biochem, D-55128 Mainz, Germany
3.Johannes Gutenberg Univ Mainz, Inst Organ Chem, D-55128 Mainz, Germany
4.Chinese Acad Sci, Kunming Inst Bot, Kunming 650204, Peoples R China

Recommended Citation:
Abbasi, R; Efferth, T; Kuhmann, C; Opatz, T; Hao, XJ; Popanda, O; Schmezer, P.The endoperoxide ascaridol shows strong differential cytotoxicity in nucleotide excision repair-deficient cells,TOXICOLOGY AND APPLIED PHARMACOLOGY,2012,259(3):302-310
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Abbasi, Rashda]'s Articles
[Efferth, Thomas]'s Articles
[Kuhmann, Christine]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Abbasi, Rashda]‘s Articles
[Efferth, Thomas]‘s Articles
[Kuhmann, Christine]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
文件名: Abbasi-2012-The endoperoxide asc.pdf
格式: Adobe PDF
此文件暂不支持浏览
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2018  中国科学院昆明植物研究所 - Feedback
Powered by CSpace