[en] 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 gamma irradiation in LN18 and U87 malignant glioma cells. Apigenin and siRNA-mediated CK2 protein depletion further inhibited NF-kappaB 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 gamma-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 gamma 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.
Disciplines :
Genetics & genetic processes
Author, co-author :
KROONEN, Jérôme ✱; Centre Hospitalier Universitaire de Liège - CHU > Centre d'oncologie
Artesi, Maria ✱; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine
CAPRARO, Valérie ; Centre Hospitalier Universitaire de Liège - CHU > Secteur biologie moléculaire
Nguyen-Khac, Minh-Tuan
Willems, Marie ; Université de Liège - ULiège > Form. doc. sc. bioméd. & pharma.
Chakravarti, Arnab
Bours, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine
Robe, Pierre ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine
✱ These authors have contributed equally to this work.
Language :
English
Title :
Casein kinase 2 inhibition modulates the DNA damage response but fails to radiosensitize malignant glioma cells.
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