Evidence map›Paper›PMID 26649750›Full record

ArticlePloS one2015

Hypoxia-Targeted Drug Q6 Induces G2-M Arrest and Apoptosis via Poisoning Topoisomerase II under Hypoxia.

Linlin Chang, Xiaowen Liu, Dandan Wang, Jian Ma, Tianyi Zhou, Ying Chen, Rong Sheng, Yongzhou Hu, Ying Du, Qiaojun He and 2 more

Abstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Trial
  2. Review
  3. Article
  4. Hypoxia-targeted drug delivery.Chemical Society reviews · 2019
    Review
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Linlin ChangZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Xiaowen LiuZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Dandan WangZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Jian MaZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Tianyi ZhouZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Ying ChenZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Rong ShengZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Yongzhou HuZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Ying DuDepartment of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Qiaojun HeZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Bo YangZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Hong ZhuZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In spite of the tremendous efforts dedicated to developing hypoxia-activated prodrugs, no agents yet have been approved for clinical therapy. In the present study, the hypoxic selective anti-cancer activity as well as the cellular target of a novel tirapazamine (TPZ) analogue, 7-methyl-3-(3-chlorophenyl)-quinoxaline-2-carbonitrile 1,4-dioxide (Q6) were investigated. Q6 implemented anti-cancer effects via poisoning topoisomerase II (topo II) under hypoxia. Modified trapped in agarose DNA immunostaining (TARDIS) assay showed more topo II-DNA cleavage complexes trapped by Q6 than TPZ at even lower concentration. In addition, by introducing ataxia-telangiectasia-mutated (ATM) kinase inhibitors caffeine and KU-60019, we displayed that Q6-triggered apoptosis was attributed, at least partially, to DNA double-strand breaks generated by the topo II-targeting effect. Collectively, Q6 stood out for its better hypoxia-selectivity and topo II-poisoning than the parental compound TPZ. All these data shed light on the research of Q6 as a promising hypoxia-activated prodrug candidate for human hepatocellular carcinoma therapy.

Indexed as

ApoptosisCarcinoma, HepatocellularCell Line, TumorDrug Delivery SystemsHumansHypoxiaLiver NeoplasmsMorpholinesThioxanthenesTopoisomerase II Inhibitors2-(2,6-dimethylmorpholin-4-yl)-N-(5-(6-morpholin-4-yl-4-oxo-4H-pyran-2-yl)-9H-thioxanthen-2-yl)acetamideMorpholinesThioxanthenesTopoisomerase II Inhibitors

Identifiers

PMID26649750
PMCPMC4674137

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.