Evidence map›Paper›PMID 27341700›Full record

ArticleCancer science2016

Nontoxic concentration of DNA-PK inhibitor NU7441 radio-sensitizes lung tumor cells with little effect on double strand break repair.

Shigeaki Sunada, Hideki Kanai, Younghyun Lee, Takeshi Yasuda, Hirokazu Hirakawa, Cuihua Liu, Akira Fujimori, Mitsuru Uesaka, Ryuichi Okayasu

Open access · goldAbstract read
In one paragraph

Article in Cancer science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.0field-weighted citation impact, top 9% of its field
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

25 citing papers in PubMed, 36 citations in OpenAlex.

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  6. Basic and translational research on carbon-ion radiobiology.American journal of cancer research · 2023
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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

9 authors at 1 institution in 1 country.

Shigeaki SunadaDepartment of Nuclear Engineering and Management, School of Engineering, University of Tokyo, Tokyo, Japan.
Hideki KanaiDepartment of Nuclear Engineering and Management, School of Engineering, University of Tokyo, Tokyo, Japan.
Younghyun LeeResearch Center for Radiation Protection, National Institute of Radiological Sciences, Chiba, Japan.
Takeshi YasudaResearch Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba, Japan.
Hirokazu HirakawaResearch Center for Radiation Protection, National Institute of Radiological Sciences, Chiba, Japan.
Cuihua LiuResearch Center for Radiation Protection, National Institute of Radiological Sciences, Chiba, Japan.
Akira FujimoriResearch Center for Radiation Protection, National Institute of Radiological Sciences, Chiba, Japan.
Mitsuru UesakaDepartment of Nuclear Engineering and Management, School of Engineering, University of Tokyo, Tokyo, Japan.
Ryuichi OkayasuResearch Center for Radiation Protection, National Institute of Radiological Sciences, Chiba, Japan. rokayasu@nirs.go.jp.
The University of Tokyo · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

High-linear energy transfer (LET) heavy ions have been increasingly employed as a useful alternative to conventional photon radiotherapy. As recent studies suggested that high LET radiation mainly affects the nonhomologous end-joining (NHEJ) pathway of DNA double strand break (DSB) repair, we further investigated this concept by evaluating the combined effect of an NHEJ inhibitor (NU7441) at a non-toxic concentration and carbon ions. NU7441-treated non-small cell lung cancer (NSCLC) A549 and H1299 cells were irradiated with X-rays and carbon ions (290 MeV/n, 50 keV/μm). Cell survival was measured by clonogenic assay. DNA DSB repair, cell cycle distribution, DNA fragmentation and cellular senescence induction were studied using a flow cytometer. Senescence-associated protein p21 was detected by western blotting. In the present study, 0.3 μM of NU7441, nontoxic to both normal and tumor cells, caused a significant radio-sensitization in tumor cells exposed to X-rays and carbon ions. This concentration did not seem to cause inhibition of DNA DSB repair but induced a significant G2/M arrest, which was particularly emphasized in p53-null H1299 cells treated with NU7441 and carbon ions. In addition, the combined treatment induced more DNA fragmentation and a higher degree of senescence in H1299 cells than in A549 cells, indicating that DNA-PK inhibitor contributes to various modes of cell death in a p53-dependent manner. In summary, NSCLC cells irradiated with carbon ions were radio-sensitized by a low concentration of DNA-PK inhibitor NU7441 through a strong G2/M cell cycle arrest. Our findings may contribute to further effective radiotherapy using heavy ions.

Indexed as

DNA Breaks, Double-StrandedCell Line, TumorCell SurvivalChromonesDNA-Activated Protein KinaseDNA RepairG2 Phase Cell Cycle CheckpointsHumansLinear Energy TransferLung NeoplasmsMorpholinesRadiation-Sensitizing Agents8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-oneChromonesDNA-Activated Protein KinaseMorpholinesRadiation-Sensitizing AgentsDNAPK proteinG2 cell cycle arrestheavy ionsnon-small cell lung cancerp53 genes

Identifiers

PMID27341700
PMCPMC5021029
OpenAlexW2516232006

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.