Abstract
We have previously documented that naked antisense CK2α ODN can potently induce apoptosis in cancer cells in culture and in mouse xenograft human prostate cancer. The effects of the antisense CK2α are related to downregulation of CK2α message and rapid loss of the CK2 from the nuclear compartment. Here we demonstrate that downregulation of CK2 elicited by diverse methods leads to inhibition of cell growth and induction of apoptosis. The various approaches to downregulation of CK2 employed were transfection with kinase-inactive plasmid, use of CK2α siRNA, use of inhibitors of CK2 activity, and use of antisense CK2α ODN packaged in sub-50 nm nanocapsules made from tenascin. In all cases, the downregulation of CK2 is associated with loss in cell survival. We have also described preliminary observations on an approach to targeting CK2 in cancer cells. For this, sub-50 nm tenascin-based nanocapsules bearing the antisense CK2α ODN were employed to test that the antisense is delivered to the cancer cells in vivo. The results provide the first preliminary evidence that such an approach may be feasible for targeting CK2 in cancer cells. Together, our results suggest that CK2 is potentially a highly plausible target for cancer therapy.
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Abbreviations
- CK2:
-
acronym for the former name casein kinase 2
- TBB:
-
4,5,6,7-tetrabromobenzotriazole
- TN:
-
tenascin
- PO:
-
phosphodiester oligonucleotide
- MO:
-
morpholino oligonucleotide
References
Ahmed K, Davis A, Wang H, Faust R, Yu S, Tawfic S: Significance of protein kinase CK2 nuclear signaling in neoplasia. J Cell Biochem Suppl 35: 130–135, 2000
Ahmed K, Gerber DA, Cochet C: Joining the cell survival squad: An emerging role for protein kinase CK2. Trends Cell Biol 12: 226–229, 2002
Litchfield DW: Protein kinase CK2: Structure, regulation and role in cellular decisions of life and death. Biochem J 369: 1–15, 2003
Guerra B, Issinger O-G: Protein kinase CK2 and its role in cellular proliferation, development, and pathology. Electrophoresis 20: 391–408, 1999
Pinna LA: Protein kinase CK2: A challenge to canons. J Cell Sci 115: 3873–3878, 2002
Tawfic S, Yu S, Wang H, Faust R, Davis A, Ahmed K: Protein kinase CK2 signal in neoplasia. Histol Histopathol 16: 573–582, 2001
Landesman-Bollag E, Song DH, Romieu-Mourez R, Sussman DJ, Cardiff RD, Sonenshein GE, Seldin DC: Protein kinase CK2: Signaling and tumorigenesis in the mammary gland. Mol Cell Biochem 227: 153–165, 2001
Landesman-Bollag E, Channavajhala PL, Cardiff RD, Seldin DC: p53 Deficiency and misexpression of protein kinase CK2α collaborate in the development of thymic lymphomas in mice. Oncogene 16: 2965–2974, 1998
Padmanabha R, Chen-Wu JLP, Hanna DE, Glover CVC: Isolation, sequencing, and disruption of the yeast CKA2 gene: Casein kinase II is essential for viability in S. cerevisiae. Mol Cell Biol 10: 4089–4099, 1990
Wang H, Davis A, Yu S, Ahmed K: Response of cancer cells to molecular interruption of the CK2 signal. Mol Cell Biochem 227: 167–174, 2001
Faust RA, Tawfic S, Davis AT, Bubash LA, Ahmed K: Antisense oligodeoxynucleotides against protein kinase CK2-α inhibit growth of squamous cell carcinoma of the head and neck in vitro. Head Neck 22: 341–346, 2000
Slaton JW, Sloper DT, Unger G, Davis A, Ahmed K: Induction of apoptosis by antisense CK2 in human prostate cancer xenograft model. Mol Cancer Res 2: 712–721, 2004
Aukhill I, Joshi P, Erickson HP: Cell- and heparin-binding domains of the hexabrachion arm identified by tenascin expression proteins. J Biol Chem 268: 2542–2553, 1993
Guo C, Yu S, Davis AT, Green JE, Ahmed K: A potential role of nuclear matrix-associated protein kinase CK2 in protection against drug-induced apoptosis in cancer cells. J Biol Chem 276: 5992–5999, 2001
Wang G, Ahmad KA, Ahmed K: Modulation of receptor mediated apoptosis by CK2. Mol Cell Biochem 274: 201–205
Ruzzene M, Penzo D, Pinna L: Protein kinase CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) induces apoptosis and caspase-dependent degradation of haematopoietic lineage cell-specific protein 1 (HS1) in Jurkat cells. Biochem J 364: 41–47, 2002
Unger GM, Davis AT, Slaton JW, Ahmed K: Protein kinase CK2 as regulator of cell survival: Implications for cancer therapy. Curr Cancer Drug Targets 4(1): 77–84, 2004
Unger G, Adams G, Davis A, Ahmed K: Effective chemotherapeutic activity by sub50-nm nanocapsules antisense to protein kinase CK2 for eradication of in vitro tumor nests via targeted caveolar mediated endocytosis. Proc AACR 43: 577, 2002
Unger G, Slaton J, Adams G, Davis A, Ahmed K: Antisense formulation via sub50 nm nanoencapsulation enhances effectiveness of problematic medicinal chemistry for tumor-specific antisense to PK CK2. Proc AACR 44(2): 6431, 2003
Yu S, Wang H, Davis A, Ahmed K: Consequences of CK2 signaling to the nuclear matrix. Mol Cell Biochem 227(1/2): 67–71, 2001
Cochet and Filhol on cell dynamics of CK2? Filhol O, Martiel J-L, Cochet C. Protein kinase CK2: A new view of an old molecular complex. EMBO Rep 5: 351–355, 2004
Tuxhorn JA, Ayala GE, Rowley DR: Reactive stroma in prostate cancer progression. J Urol 166: 2472–2483, 2001
Anderson RGW: The caveolae membrane system. Annu Rev Biochem 67: 199–225, 1999
Kato K, Yashuhiro H, Miyamoto M, Katoh H: Overexpression of caveolin-1 in esophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage. Cancer 94: 929–933, 2002
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Wang, G., Unger, G., Ahmad, K.A. et al. Downregulation of CK2 induces apoptosis in cancer cells – A potential approach to cancer therapy. Mol Cell Biochem 274, 77–84 (2005). https://doi.org/10.1007/s11010-005-3077-1
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DOI: https://doi.org/10.1007/s11010-005-3077-1