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

Zhao,Tiesuo; Jia,Huijie; Li,Lifei; Zhang,Guoliang; Zhao,Min; Cheng,Qian; Zheng,Junnian; Li,Di

doi:10.3892/or.2013.2407

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

Authors:
- Tiesuo Zhao
- Huijie Jia
- Lifei Li
- Guoliang Zhang
- Min Zhao
- Qian Cheng
- Junnian Zheng
- Di Li
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Affiliations: Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China, Laboratory of Transplantation and Immunology, Xuzhou Medical College, Xuzhou, Jiangsu 221000, P.R. China, Department of Respiration, Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia 028007, P.R. China, Department of Laboratory Medicine, Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia 028007, P.R. China, Department of Anatomy, The Medical College of Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia 028000, P.R. China
Published online on: April 18, 2013 https://doi.org/10.3892/or.2013.2407
Pages: 377-384

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Abstract

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.

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1	Greenlee RT, Hill-Harmon MB, Murray T and Thun M: Cancer statistics, 2001. CA Cancer J Clin. 51:15–36. 2001. View Article : Google Scholar
2	Riley PA: Free radicals in biology: oxidative stress and the effects of ionizing radiation. Int J Radiat Biol. 65:27–33. 1994. View Article : Google Scholar : PubMed/NCBI
3	Lentine B, Antonucci L, Hunce R, Edwards J, Marallano V and Krucher NA: Dephosphorylation of threonine-821 of the retinoblastoma tumor suppressor protein (Rb) is required for apoptosis induced by UV and Cdk inhibition. Cell Cycle. 11:3324–3330. 2012. View Article : Google Scholar : PubMed/NCBI
4	Choi YJ, Kim YJ, Lee JW, Lee Y, Lim YB and Chung HW: Cyto-/genotoxic effect of CdSe/ZnS quantum dots in human lung adenocarcinoma cells for potential photodynamic UV therapy applications. J Nanosci Nanotechnol. 12:2160–2168. 2012. View Article : Google Scholar : PubMed/NCBI
5	Huang J, Zhang L, Liu W, et al: CCDC134 interacts with hADA2a and functions as a regulator of hADA2a in acetyltransferase activity, DNA damage-induced apoptosis and cell cycle arrest. Histochem Cell Biol. 138:41–55. 2012. View Article : Google Scholar : PubMed/NCBI
6	Cao C, Lu S, Kivlin R, et al: AMP-activated protein kinase contributes to UV- and H₂O₂-induced apoptosis in human skin keratinocytes. J Biol Chem. 283:28897–28908. 2008. View Article : Google Scholar : PubMed/NCBI
7	Kyriakis JM and Avruch J: Protein kinase cascades activated by stress and inflammatory cytokines. Bioessays. 18:567–577. 1996. View Article : Google Scholar : PubMed/NCBI
8	Johnson GL and Lapadat R: Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 298:1911–1912. 2002. View Article : Google Scholar : PubMed/NCBI
9	Seo M, Cho CH, Lee YI, et al: Cdc42-dependent mediation of UV-induced p38 activation by G protein betagamma subunits. J Biol Chem. 279:17366–17375. 2004. View Article : Google Scholar : PubMed/NCBI
10	Kato T Jr, Delhase M, Hoffmann A and Karin M: CK2 is a C-terminal IkappaB kinase responsible for NF-kappaB activation during the UV response. Mol Cell. 12:829–839. 2003. View Article : Google Scholar : PubMed/NCBI
11	Roux PP and Blenis J: ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev. 68:320–344. 2004. View Article : Google Scholar : PubMed/NCBI
12	Keller DM, Zeng X, Wang Y, et al: A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1. Mol Cell. 7:283–292. 2001. View Article : Google Scholar
13	Jacks KA and Koch CA: Differential regulation of mitogen- and stress-activated protein kinase-1 and -2 (MSK1 and MSK2) by CK2 following UV radiation. J Biol Chem. 285:1661–1670. 2010. View Article : Google Scholar : PubMed/NCBI
14	Sayed M, Kim SO, Salh BS, Issinger OG and Pelech SL: Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase. J Biol Chem. 275:16569–16573. 2000. View Article : Google Scholar : PubMed/NCBI
15	Scaglioni PP, Yung TM, Cai LF, et al: A CK2-dependent mechanism for degradation of the PML tumor suppressor. Cell. 126:269–283. 2006. View Article : Google Scholar : PubMed/NCBI
16	Landesman-Bollag E, Song DH, Romieu-Mourez R, et al: Protein kinase CK2: signaling and tumorigenesis in the mammary gland. Mol Cell Biochem. 227:153–165. 2001. View Article : Google Scholar : PubMed/NCBI
17	Giroux V, Dagorn JC and Iovanna JL: A review of kinases implicated in pancreatic cancer. Pancreatology. 9:738–754. 2009. View Article : Google Scholar : PubMed/NCBI
18	Ruzzene M and Pinna LA: Addiction to protein kinase CK2: a common denominator of diverse cancer cells? Biochim Biophys Acta. 1804:499–504. 2010. View Article : Google Scholar : PubMed/NCBI
19	Trembley JH, Wang G, Unger G, Slaton J and Ahmed K: Protein kinase CK2 in health and disease: CK2: a key player in cancer biology. Cell Mol Life Sci. 66:1858–1867. 2009. View Article : Google Scholar : PubMed/NCBI
20	Ahmed K, Davis AT, Wang H, et al: Significance of protein kinase CK2 nuclear signaling in neoplasia. J Cell Biochem (Suppl). 35:130–135. 2000. View Article : Google Scholar : PubMed/NCBI
21	Piazza F, Manni S, Ruzzene M, et al: Protein kinase CK2 in hematologic malignancies: reliance on a pivotal cell survival regulator by oncogenic signaling pathways. Leukemia. 26:1174–1179. 2012. View Article : Google Scholar : PubMed/NCBI
22	Pinna LA: Protein kinase CK2: a challenge to canons. J Cell Sci. 115:3873–3878. 2002. View Article : Google Scholar : PubMed/NCBI
23	Ahmed K, Gerber DA and Cochet C: Joining the cell survival squad: an emerging role for protein kinase CK2. Trends Cell Biol. 12:226–230. 2002. View Article : Google Scholar : PubMed/NCBI
24	Manni S, Brancalion A, Tubi LQ, et al: Protein kinase CK2 protects multiple myeloma cells from ER stress-induced apoptosis and from the cytotoxic effect of HSP90 inhibition through regulation of the unfolded protein response. Clin Cancer Res. 18:1888–1900. 2012. View Article : Google Scholar
25	Pustisek N and Situm M: UV-radiation, apoptosis and skin. Coll Antropol. 35(Suppl 2): 339–341. 2011.
26	Zandi S, Kalia S and Lui H: UVA1 phototherapy: a concise and practical review. Skin Therapy Lett. 17:1–4. 2012.PubMed/NCBI
27	Tomas D: Apoptosis, UV-radiation, precancerosis and skin tumors. Acta Med Croatica. 63(Suppl 2): 53–58. 2009.(In Croatian).
28	Lee WR, Shen SC, Lin HY, et al: Wogonin and fisetin induce apoptosis in human promyeloleukemic cells, accompanied by a decrease of reactive oxygen species, and activation of caspase 3 and Ca(2+)-dependent endonuclease. Biochem Pharmacol. 63:225–236. 2002.PubMed/NCBI
29	Sarno S, Reddy H, Meggio F, et al: Selectivity of 4,5,6,7-tetrabromobenzotriazole, an ATP site-directed inhibitor of protein kinase CK2 (‘casein kinase-2’). FEBS Lett. 496:44–48. 2001.
30	Bernardi R and Pandolfi PP: Structure, dynamics and functions of promyelocytic leukaemia nuclear bodies. Nat Rev Mol Cell Biol. 8:1006–1016. 2007. View Article : Google Scholar : PubMed/NCBI
31	Scaglioni PP, Yung TM, Choi S, Baldini C, et al: CK2 mediates phosphorylation and ubiquitin-mediated degradation of the PML tumor suppressor. Mol Cell Biochem. 316:149–154. 2008. View Article : Google Scholar : PubMed/NCBI
32	de Stanchina E, Querido E, Narita M, et al: PML is a direct p53 target that modulates p53 effector functions. Mol Cell. 13:523–535. 2004.PubMed/NCBI
33	Lavau C, Marchio A, Fagioli M, et al: The acute promyelocytic leukaemia-associated PML gene is induced by interferon. Oncogene. 11:871–876. 1995.PubMed/NCBI