Evidence map›Paper›PMID 21310046›Full record

ArticleRadiation oncology (London, England)2011

A specific inhibitor of protein kinase CK2 delays gamma-H2Ax foci removal and reduces clonogenic survival of irradiated mammalian cells.

Felix Zwicker, Maren Ebert, Peter E Huber, Jürgen Debus, Klaus-Josef Weber

Open access · goldAbstract read
In one paragraph

Article in Radiation oncology (London, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

11 citing papers in PubMed, 21 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Targeting protein kinase CK2 in the treatment of cholangiocarcinoma.Exploration of targeted anti-tumor therapy · 2021
    Review
  5. Article
  6. Article
  7. Article
  8. Dichloroacetate induces tumor-specific radiosensitivity in vitro but attenuates radiation-induced tumor growth delay in vivo.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2013
    Article
  9. [Protein kinase CK2 and human malignant tumors].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2012
    Review
  10. Article
  11. In vivo (Athens, Greece)
    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

5 authors at 1 institution in 1 country.

Felix ZwickerDepartment of Radiation Oncology, University of Heidelberg, Heidelberg, Germany. f.zwicker@dkfz.de
Maren Ebert
Peter E Huber
Jürgen Debus
Klaus-Josef Weber
Heidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe protein kinase CK2 sustains multiple pro-survival functions in cellular DNA damage response and its level is tightly regulated in normal cells but elevated in cancers. Because CK2 is thus considered as potential therapeutic target, DNA double-strand break (DSB) formation and rejoining, apoptosis induction and clonogenic survival was assessed in irradiated mammalian cells upon chemical inhibition of CK2.

methodsMRC5 human fibroblasts and WIDR human colon carcinoma cells were incubated with highly specific CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB), or mock-treated, 2 hours prior to irradiation. DSB was measured by pulsed-field electrophoresis (PFGE) as well as gamma-H2AX foci formation and removal. Apoptosis induction was tested by DAPI staining and sub-G1 flow cytometry, survival was quantified by clonogenic assay.

resultsTBB treatment did not affect initial DNA fragmention (PFGE; up to 80 Gy) or foci formation (1 Gy). While DNA fragment rejoining (PFGE) was not inhibited by the drug, TBB clearly delayed gamma-H2AX foci disappearence during postirradiation incubation. No apoptosis induction could be detected for up to 38 hours for both cell lines and exposure conditions (monotherapies or combination), but TBB treatment at this moderately toxic concentration of 20 μM (about 40% survival) enhanced radiation-induced cell killing in the clonogenic assay.

conclusionsThe data imply a role of CK2 in gamma-H2AX dephosporylation, most likely through its known ability to stimulate PP2A phosphatase, rather than DSB rejoining. The slight but definite clonogenic radiosensitization by TBB does apparently not result from interference with an apoptosis suppression function of CK2 in these cells but could reflect inhibitor-induced uncoupling of DNA damage response decay from break ligation.

Indexed as

AnimalsCasein Kinase IICells, CulturedCell SurvivalDNA Breaks, Double-StrandedDNA RepairDrug Evaluation, PreclinicalFibroblastsHistonesHumansMammalsNeoplastic Stem CellsProtein Kinase InhibitorsSubstrate SpecificityTime FactorsTriazoles4,5,6,7-tetrabromobenzotriazoleCasein Kinase IIH2AX protein, humanHistonesProtein Kinase InhibitorsTriazoles

Identifiers

PMID21310046
PMCPMC3045342
OpenAlexW2100809340

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.