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.