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Inhibition of casein kinase 2 enhances the death ligand- and natural kiler cell-induced hepatocellular carcinoma cell death

Authors
 H.-R. Kim  ;  K. Kim  ;  K.-H. Lee  ;  S. J. Kim  ;  J. Kim 
Citation
 CLINICAL AND EXPERIMENTAL IMMUNOLOGY, Vol.152(2) : 336-344, 2008 
Journal Title
 CLINICAL AND EXPERIMENTAL IMMUNOLOGY 
ISSN
 0009-9104 
Issue Date
2008
MeSH
Apoptosis/drug effects ; Apoptosis/immunology ; Carcinoma, Hepatocellular/immunology ; Carcinoma, Hepatocellular/pathology* ; Casein Kinase II/antagonists & inhibitors* ; Casein Kinase II/physiology ; Cytoplasmic Granules/immunology ; Cytotoxicity, Immunologic/drug effects ; Cytotoxicity, Immunologic/immunology ; Emodin/pharmacology ; Fas Ligand Protein/immunology ; Humans ; Killer Cells, Natural/immunology* ; Liver Neoplasms/immunology ; Liver Neoplasms/pathology* ; Protein Kinase Inhibitors/pharmacology ; Recombinant Proteins/immunology ; TNF-Related Apoptosis-Inducing Ligand/immunology ; Tumor Cells, Cultured
Keywords
Apoptosis/drug effects ; Apoptosis/immunology ; Carcinoma, Hepatocellular/immunology ; Carcinoma, Hepatocellular/pathology* ; Casein Kinase II/antagonists & inhibitors* ; Casein Kinase II/physiology ; Cytoplasmic Granules/immunology ; Cytotoxicity, Immunologic/drug effects ; Cytotoxicity, Immunologic/immunology ; Emodin/pharmacology ; Fas Ligand Protein/immunology ; Humans ; Killer Cells, Natural/immunology* ; Liver Neoplasms/immunology ; Liver Neoplasms/pathology* ; Protein Kinase Inhibitors/pharmacology ; Recombinant Proteins/immunology ; TNF-Related Apoptosis-Inducing Ligand/immunology ; Tumor Cells, Cultured
Abstract
Recent studies have shown that the inhibition of casein kinase 2 (CK2) sensitizes many cancer cells to Fas ligand- and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. However, it has not been demonstrated directly whether CK2 inhibition can also enhance the cytotoxicity of natural killer (NK) cells, which actually use the death ligands to kill cancer cells in vivo. To address whether NK cell-mediated cancer cell death is affected by the inhibition of CK2, we first checked whether the death ligand-induced apoptosis of hepatocellular carcinoma cells (HCCs) and HeLa were affected by CK2 inhibition. We then investigated the effect of CK2 inhibition on NK cytotoxicity against HCCs and HeLa cells and its mechanistic features. Inhibition of CK2 by emodin increased the apoptotic cell death of HepG2, Hep3B and HeLa when the cancer cell lines were treated with a soluble form of recombinant TRAIL or an agonistic antibody of Fas. This phenomenon appeared to be correlated with the expression level of death receptors on the cancer cell surface. More interestingly, the inhibition of CK2 also greatly increased the NK cell-mediated cancer cell killing. The NK cytotoxicity against the cancer cells increased about twofold when the target cells were pretreated with a specific CK2 inhibitor, emodin or 4,5,6,7-tetrabromobenzotriazole. Furthermore, the increase of the NK cytotoxicity against cancer cells by CK2 inhibition was granule-independent and mediated possibly by the death ligands on the NK cell surface. This suggests that CK2 inhibitors could be used to enhance the cytotoxicity of NK cells and consequently increase host tumour immunity.
Files in This Item:
T200803130.pdf Download
DOI
10.1111/j.1365-2249.2008.03622.x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kun Hong(김건홍) ORCID logo https://orcid.org/0000-0001-5639-6372
Kim, Se Jong(김세종)
Kim, Jong Sun(김종선) ORCID logo https://orcid.org/0000-0002-3149-669X
Kim, Hyung Ran(김형란)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108063
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