ROLE OF TOPOISOMERASE II IN NBQ MEDIATED TUMOR CELL DIFFERENTIATION
拓扑异构酶 II 在 NBQ 介导的肿瘤细胞分化中的作用
基本信息
- 批准号:6107344
- 负责人:
- 金额:$ 12.07万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1998
- 资助国家:美国
- 起止时间:1998-08-01 至 1999-07-31
- 项目状态:已结题
- 来源:
- 关键词:DNA damage DNA topoisomerases antineoplastics cell cycle cell differentiation chemical cleavage clone cells cytotoxicity densitometry drug design /synthesis /production drug screening /evaluation enzyme inhibitors flow cytometry neoplastic cell nucleic acid sequence physical chemical interaction polymerase chain reaction quinoline analog
项目摘要
3-nitrobenzothiazolo[3,2-a] quinolinium (NBQ) intercalates in DNA and
shows a strong potential as antitumor agent. Studies in our laboratory on
its mode of action revealed that the cytotoxicity of NBQ is associated with
topoisomerase II- mediated DNA strand breaks. Moreover, NBQ significantly
enhances in vivo lens regeneration in the adult newt Notophtalmus
viridescens, and induces in vitro the differentiation of HL-60 and DFaDu
tumor cell lines. NBQ, at non-lethal doses that stimulate differentiation,
binds in vitro topoisomerase II to purified DNA.
The involvement of topoisomerase II in the cytotoxic and differentiation
activities of NBQ, brings into question what is the role of topoisomerase
II in the NBQ-induced differentiation. Knowledge of the molecular
mechanism(s) through which NBQ induces differentiation, in contrast to its
cytotoxic effect, will further a potentially new mode of cancer
chemotherapy. To explore this question, we will study the effects of NBQ
and eight analogs using a combination of molecular and cellular approaches.
Because the DNA sequence localization of the cleavable complex, formed by
NBQ and the various analogs, with topoisomerase II should be identical, the
comparison of drug effects is more amenable to interpretation. We propose
to characterize the cytotoxic activity of the eight NBQ analogues and
evaluate athe inhibition f topoisomerase activity. The differentiation
ability of each analog will compared to NBQ (80 - 90% HL-60 cells
differentiated into the granulocytic series). To understand the mechanism
of action of NBQ and analogs, we will evaluate; the formation of protein
linked strand breaks in intact cells, the inhibition of topoisomerase
activity i vitro, and promotion of chromosomal abnormalities. The effects
of NBQ analogs on the cell cycle will be detected at concentration that
induce differentiation compared with cytotoxic concentrations. The pattern
of topoisomerase II-mediated DNA cleavage stimulated by NBQ will be
compared to the cleavage pattern stimulated by NBQ analogs and the
topoisomerase II poisons doxorubicin, VP-16 and m-AMSA. Finally, the
effects of NBQ analogs will be studied in the resistant HL-60 and m-AMSA.
Finally, the effects of NBQ analogs will be studied in the resistant HL-60
cell line (HL-60/NBA), which allows us to study the basis for differences
in activity, specially, the induction of differentiation.
3-硝基苯并噻唑[3,2-a]喹啉(NBQ)插入DNA和
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
ADRIANA BAEZ其他文献
ADRIANA BAEZ的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('ADRIANA BAEZ', 18)}}的其他基金
ROLE OF TOPOISOMERASE II IN NBQ MEDIATED TUMOR CELL DIFFERENTIATION
拓扑异构酶 II 在 NBQ 介导的肿瘤细胞分化中的作用
- 批准号:
6216591 - 财政年份:1999
- 资助金额:
$ 12.07万 - 项目类别:
ROLE OF TOPOISOMERASE II IN NBQ MEDIATED TUMOR CELL DIFFERENTIATION
拓扑异构酶 II 在 NBQ 介导的肿瘤细胞分化中的作用
- 批准号:
6271688 - 财政年份:1998
- 资助金额:
$ 12.07万 - 项目类别:
ROLE OF TOPOISOMERASE II IN NBQ MEDIATED TUMOR CELL DIFFERENTIATION
拓扑异构酶 II 在 NBQ 介导的肿瘤细胞分化中的作用
- 批准号:
6240291 - 财政年份:1997
- 资助金额:
$ 12.07万 - 项目类别:
UPR--MEDICAL SCIENCES CAMPUS, MBRS PROGRAM
UPR--医学科学校区,MBRS 项目
- 批准号:
2873279 - 财政年份:1985
- 资助金额:
$ 12.07万 - 项目类别:
U P R MEDICAL SCIENCES CAMPUS MBRS PROGRAM
UP R 医学科学校区 MBRS 项目
- 批准号:
3513569 - 财政年份:1985
- 资助金额:
$ 12.07万 - 项目类别:
相似海外基金
Understanding and exploiting DNA topoisomerases in cancer biology
了解和利用癌症生物学中的 DNA 拓扑异构酶
- 批准号:
10296437 - 财政年份:2021
- 资助金额:
$ 12.07万 - 项目类别:
Understanding and exploiting DNA topoisomerases in cancer biology
了解和利用癌症生物学中的 DNA 拓扑异构酶
- 批准号:
10473793 - 财政年份:2021
- 资助金额:
$ 12.07万 - 项目类别:
Structural and mechanistic analysis of type II DNA topoisomerases
II 型 DNA 拓扑异构酶的结构和机制分析
- 批准号:
2059935 - 财政年份:2018
- 资助金额:
$ 12.07万 - 项目类别:
Studentship
Conference: 2016 Gordon Research Seminar on DNA Topoisomerases to be held at Sunday River in Newry, ME on August 6-7, 2016
会议:2016 年戈登 DNA 拓扑异构酶研究研讨会将于 2016 年 8 月 6 日至 7 日在缅因州纽里的 Sunday River 举行
- 批准号:
1643077 - 财政年份:2016
- 资助金额:
$ 12.07万 - 项目类别:
Standard Grant
2014 DNA Topoisomerases in Biology and Medicine Gordon Research Conference
2014 DNA 拓扑异构酶在生物学和医学戈登研究会议
- 批准号:
8714782 - 财政年份:2014
- 资助金额:
$ 12.07万 - 项目类别:
Biochemical Analyses of Type II DNA Topoisomerases
II 型 DNA 拓扑异构酶的生化分析
- 批准号:
7909236 - 财政年份:2009
- 资助金额:
$ 12.07万 - 项目类别:
DNA Topoisomerases and DNA Topology in E. coli
大肠杆菌中的 DNA 拓扑异构酶和 DNA 拓扑
- 批准号:
0090880 - 财政年份:2001
- 资助金额:
$ 12.07万 - 项目类别:
Continuing Grant