Inhibition of CK2 enhances UV-triggered apoptotic cell death in lung cancer cell lines

Lung cancer is a high-grade malignancy with poor 5 year-survival rates that remains incurable with current therapies. Different cellular stresses, including antitumor agents, ionizing radiation and ultraviolet (UV) light, can induce apoptosis and activate signaling pathways. UV has multiple effects on tumor cells, including DNA damage, and increases the expression of some genes involved in tumor cell apoptosis and DNA repair. It has been reported that UV can also activate casein kinase 2 (CK2). CK2, a Ser/Thr protein kinase, has been reported to be frequently overexpressed in various types of human cancer, including lung cancer, and is associated with tumor development. Thus, combination of UV and CK2 inhibitors may be a new strategy for the treatment of lung cancer. Our results demonstrated that inhibition of CK2a through CK2 siRNA or a CK2 inhibitor [(4,5,6,7-tetrabromobenzotriazole (TBB)] enhances the decrease in cell viability of lung cancer cells (A549 and H2030) induced by UV. Western blot analysis demonstrated that the combination increased the expression of apoptotic protein markers cytochrome c and the cleavage of poly ADP-ribose polymerase (PARP) and caspase-3. Furthermore, our results indicated that UV decreased the expression of the tumor suppressor protein PML through activation of CK2. Inhibition of CK2 by CK2 siRNA and TBB can recover the reduction of PML induced by UV. Collectively, these results demonstrate the significant apoptosis of lung cancer cells induced by combination treatment of the CK2 inhibitor and UV radiation. CK2 enhanced cell apoptosis by UV radiation may due, at least partly, to recover the expression of PML. These findings warrant the clinical testing of CK2 inhibitors which, when used in conjunction with DNA-damaging agents such as radiation, may be an effective cancer therapeutic strategy.