Protein kinase CK2 is a highly ubiquitous and conserved protein serine/threonine kinase that has been found to be involved not only in cell growth and proliferation, but also in suppression of apoptosis. CK2 is capable of dynamic intracellular shuttling in response to a variety of signals. It is localized in both the nucleus and cytoplasm in normal cells, but is particularly predominant in the nuclear compartment in cancer cells. CK2 has been found to be uniformly dysregulated in all the cancers that have been examined. Downregulation of CK2 by chemical or molecular methods promotes apoptosis in cells. We have shown that antisense CK2α is particularly potent in inducing apoptosis in cancer cells in culture as well as in xenograft models of cancer such as prostate cancer and squamous cell carcinoma of head and neck. The antisense CK2α oligodeoxynucleotide (ODN) mediates tumor cell death in a dose- and time-dependent manner such that at an appropriate concentration of the antisense, a complete resolution of the xenograft tumor is observed. Interestingly, normal and benign cells (in culture as well as in vivo) demonstrate a relative resistance to the antisense CK2α ODN treatment, which raises the possibility of a significant therapeutic window for this therapy. Further, novel approaches such as the delivery of antisense CK2α ODN encapsulated in sub-50-nm tenascin nanocapsules have become available for its targeting specifically in cancer cells. Our studies minimize generally held concerns regarding suitability of CK2 as a target for cancer therapy and provide the first encouraging results for potential future application of this approach for cancer therapy.
aCellular and Molecular Biochemistry Research Laboratory, Minneapolis Veterans Affairs Medical Center
bDepartment of Laboratory Medicine and Pathology
cDepartment of Urologic Surgery
dCancer Center, University of Minnesota, Minneapolis, Minnesota, USA
eGeneSegues, Chaska, Minnesota, USA
Sponsorship: This work is supported in part by grant CA-15062 from the National Cancer Institute, Department of Health and Human Resources, and in part by the Medical Research Fund from the US Department of Veterans Affairs.
Correspondence to K. Ahmed, Cellular and Molecular Biochemistry Research Laboratory (151), Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, Minnesota 55417, USA
Tel: +1 612 467-2594; fax: +1 612 725-2093;
Received 15 July 2005 Accepted 25 July 2005