Casein kinase 2 inhibition modulates the DNA damage response but fails to radiosensitize malignant glioma cells

Kroonen,Jérôme; Artesi,Maria; Capraro,Valérie; Nguyen-Khac,Minh-Tuan; Willems,Marie; Chakravarti,Arnab; Bours,Vincent; Robe,Pierre  A.

doi:10.3892/ijo.2012.1489

Casein kinase 2 inhibition modulates the DNA damage response but fails to radiosensitize malignant glioma cells

Authors:
- Jérôme Kroonen
- Maria Artesi
- Valérie Capraro
- Minh-Tuan Nguyen-Khac
- Marie Willems
- Arnab Chakravarti
- Vincent Bours
- Pierre A. Robe
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Affiliations: Department of Human Genetics and GIGA Research Center, University of Liège, 4000 Liege, Belgium, Department of Neurosurgery, University of Liège, 4000 Liege, Belgium, Department of Radiation Oncology and James Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA, Department of Neurosurgery and Integrated Cancer Center, University Medical Center of Utrecht, 3584 CX Utrecht, The Netherlands
Published online on: May 18, 2012 https://doi.org/10.3892/ijo.2012.1489
Pages: 776-782

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Abstract

Inhibitors of casein kinase 2 (CK2), a regulator of cell proliferation and mediator of the DNA damage response, are being evaluated in clinical trials for the treatment of cancers. Apigenin was capable of inhibiting the activation of CK2 following γ irradiation in LN18 and U87 malignant glioma cells. Apigenin and siRNA-mediated CK2 protein depletion further inhibited NF-κB activation and altered the Tyr68 phosphorylation of Chk2 kinase, a DNA damage response checkpoint kinase, following irradiation. However, CK2 inhibition did not decrease the ability of these glioma cells to repair double-strand DNA breaks, as assessed by COMET assays and γ-H2Ax staining. Likewise, apigenin and siRNA-induced depletion of CK2 failed to sensitize glioma cells to the cytotoxic effect of 2 to 10 G-rays of γ irradiation, as assessed by clonogenic assays. These results contrast with those found in other cancer types, and urge to prudence regarding the inclusion of malignant glioma patients in clinical trials that assess the radiosensitizing role of CK2 inhibitors in solid cancers.

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