The effect of ionizing radiation on the subcellular localization and kinase activity of protein kinase CK2 in human non-small cell lung cancer cells

Abstract

Protein kinase CK2 is a ubiquitously expressed kinase in eukaryotes, which is known to phosphorylate many protein substrates. Because CK2 is involved in the regulation of various signaling pathways, we wondered whether CK2 participated in the regulation of ionizing radiation (IR) induced biological process. In this study, we investigated the effect of IR on the subcellular localization and kinase activity in human non-small cell lung cancer (NSCLC) cells. Immunofluorescent results showed that CK2 subunits shuttle into the nucleus mostly beginning 1 h after IR and lasting more than 6 h. We also conducted in vitro kinase assay and observed an increase in CK2 kinase activity at 6 h after IR. Furthermore, an increase in S phase was observed at 6 h after IR. Colony formation assay results demonstrated that CK2 inhibitor CX-4945 significantly enhanced the effect of irradiation in NSCLC cells. These results indicated that CK2 may be implicated in the regulation of IRinduced biological process.

Role of CK2 inhibitor CX-4945 in anti-cancer combination therapy – potential clinical relevance

“…Literature data show the versatility of CX-4945 to synergistically cooperate with various chemotherapeutics directed against different targets such as DNA, kinases, structural components of the cytoskeleton and the proteasome, endowed with specific modes of action. For example, several of the studies mentioned in this review highlighted the efficacy of combining CX-4945 with different DNA-damaging agents [48,51,52,55,57,58,61]. Indeed, it is well-known that CK2 plays an essential role in preserving genome integrity by targeting XRCC1 and XRCC4, key players in DNA single-and double-strand break repair, as well as many other proteins involved at different levels in the fine-tuned process of DNA repair, such as MGMT, MDC1 and Rad51 [25].…”

“…Recently, the feasibility of combining CX-4945-mediated CK2 inhibition with non-pharmacological anti-cancer treatments has been suggested. Indeed, pre-treating both A549 and H460 lung cancer cells with CX-4945, prior to X-ray exposure, increased their sensitivity to ionizing radiation, thereby significantly affecting the abilities of the cells to proliferate and form colonies [61].…”

The Role of Protein Kinase CK2 in Development and Disease Progression: A Critical Review

“…In addition, there is an increase in the kinase activity of CK2 during the S phase when cells are exposed to IR. Furthermore, with the pharmacological inhibition of CK2, there is an increase in IR sensitivity [ 141 , 142 ]. This emphasizes the role of CK2 in transmitting radiation stimuli to the nucleus and its involvement in the DNA damage response.…”