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.
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.
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11 citing papers in PubMed, 21 citations in OpenAlex.
- In vivo measurement of dose distribution in patients' lymphocytes: helical tomotherapy versus step-and-shoot IMRT in prostate cancer.Journal of radiation research · 2015Trial
- Serine Starvation Modulates mRNA Splicing through Translational Inhibition of SRSF Proteins.Cancer research · 2026Article
- Targeting CK2 eliminates senescent cells and prolongs lifespan in Zmpste24-deficient mice.Cell death & disease · 2024Article
- Targeting protein kinase CK2 in the treatment of cholangiocarcinoma.Exploration of targeted anti-tumor therapy · 2021Review
- CDK1 inhibition sensitizes normal cells to DNA damage in a cell cycle dependent manner.Cell cycle (Georgetown, Tex.) · 2018Article
- Streamlined preparation of genomic DNA in agarose plugs for pulsed-field gel electrophoresis.Journal of biological methods · 2018Article
- Association of protein kinase CK2 inhibition with cellular radiosensitivity of non-small cell lung cancer.Scientific reports · 2017Article
- 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] · 2013Article
- [Protein kinase CK2 and human malignant tumors].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2012Review
- Biological in-vivo measurement of dose distribution in patients' lymphocytes by gamma-H2AX immunofluorescence staining: 3D conformal- vs. step-and-shoot IMRT of the prostate gland.Radiation oncology (London, England) · 2011Article
- Article
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5 authors at 1 institution in 1 country.
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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.
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