title: Casein kinase 2 inhibition modulates the DNA damage response but fails             to radiosensitize malignant glioma cells.
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.
authors.affiliation: Department of Human Genetics and GIGA Research Center, University of Liège, Liege, Belgium.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Kroonen
authors.forename: Maria
authors.initials: M
authors.lastname: Artesi
authors.forename: Valérie
authors.initials: V
authors.lastname: Capraro
authors.forename: Minh-Tuan
authors.initials: MT
authors.lastname: Nguyen-Khac
authors.forename: Marie
authors.initials: M
authors.lastname: Willems
authors.forename: Arnab
authors.initials: A
authors.lastname: Chakravarti
authors.forename: Vincent
authors.initials: V
authors.lastname: Bours
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Robe
mesh_terms: D000704:Analysis of Variance; D047310:Apigenin / Q000494:pharmacology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004789:Enzyme Activation / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D018709:Statistics, Nonparametric
chemical_list: D016328:NF-kappa B; D011838:Radiation-Sensitizing Agents; D047310:Apigenin; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases