In VitroCharacterization of the Bacteria-derived Hypoxia-selective Cytotoxin BE-43547

克隆形成试验 缺氧(环境) 细胞毒性 药理学 IC50型 体外 肿瘤缺氧 生物 效力 细胞培养 化学 生物化学 氧气 内科学 医学 遗传学 有机化学 放射治疗
作者
Morten Busk,PETER P. EGGERTSEN,Jens Overgaard,Michael R. Horsman,Thomas Tørring,Kristian M. Jacobsen,Thomas B. Poulsen
出处
期刊:Anticancer Research [International Institute of Anticancer Research (IIAR) Conferences 1997. Athens, Greece. Abstracts]
卷期号:43 (12): 5319-5329
标识
DOI:10.21873/anticanres.16735
摘要

Hypoxia-activated pro-drugs, such as TH-302, may kill hypoxic treatment-resistant tumor cells, but have failed in clinical trials. This may be related to variable levels of drug-activating reductases. Compounds such as bacteria-derived BE-43547, which target hypoxic cells independently of reductases, may be beneficial. This study characterized the in vitro potency and hypoxia selectivity of BE-43547 and TH-302.Tumor cells were exposed to different oxygenation levels in the presence/absence of drug, and survival was quantified using total cell number (BE-43547) or clonogenic survival (BE-43547 and TH-302) assays. Half-maximal inhibitory concentration (IC50) values and the hypoxia-cytotoxicity-ratio (HCR: normoxic IC50/hypoxic IC50) were determined from dose-response curves. Finally, both drugs were tested in spheroids exposed to 20% or 0% O2 for 24 h followed by assessment of clonogenic survival.BE-43547 was highly potent and displayed little inter-cell line variability. Strongly enhanced cytotoxicity was observed under oxygen-restricted conditions with HCR's of ~100 and ~20 after 24 h of treatment with 0 or 0.5% O2, respectively. Reducing treatment time somewhat reduced hypoxia selectivity. Hypoxia selectivity was observed regardless of whether the drug was added before or during the hypoxic challenge. TH-302 IC50 values varied 10-fold under oxic conditions, whereas those of the anoxic-to-normoxic HCR varied from 15 to 88. Both BE-43547 and TH-302 were unable to completely sterilize anoxic incubated spheroids.BE-43547 is highly hypoxia-selective, and unlike TH-302, displayed minimal variability between cell lines, suggesting that BE-43547 targets a fundamental feature/target that is only present, or of survival importance, during hypoxia. Spheroid experiments suggested inadequate tissue penetrability, which may be overcome by designing novel drug analogs.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
blank完成签到,获得积分20
1秒前
1秒前
ohh发布了新的文献求助10
1秒前
bjyx完成签到,获得积分10
2秒前
852应助沈彬彬采纳,获得10
2秒前
隐形曼青应助w_x_x采纳,获得10
3秒前
3秒前
4秒前
4秒前
4秒前
大老黑发布了新的文献求助10
5秒前
5秒前
6秒前
6秒前
6秒前
江子发布了新的文献求助10
7秒前
深情安青应助ohh采纳,获得10
7秒前
8秒前
chensiyao发布了新的文献求助10
9秒前
羊肉发布了新的文献求助10
9秒前
寒染雾发布了新的文献求助10
10秒前
诸道罡发布了新的文献求助10
10秒前
11秒前
leez发布了新的文献求助10
12秒前
吴建文完成签到 ,获得积分10
12秒前
12秒前
拉塞尔....完成签到,获得积分10
12秒前
13秒前
量子星尘发布了新的文献求助10
13秒前
13秒前
15秒前
大老黑完成签到,获得积分10
15秒前
15秒前
health__up完成签到,获得积分10
15秒前
bkagyin应助江子采纳,获得10
15秒前
leez完成签到,获得积分10
17秒前
诸道罡完成签到,获得积分10
18秒前
18秒前
洋洋发布了新的文献求助10
18秒前
超帅凡阳发布了新的文献求助10
19秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Economic Geography and Public Policy 900
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3988786
求助须知:如何正确求助?哪些是违规求助? 3531116
关于积分的说明 11252493
捐赠科研通 3269766
什么是DOI,文献DOI怎么找? 1804771
邀请新用户注册赠送积分活动 881870
科研通“疑难数据库(出版商)”最低求助积分说明 809021