Targeting CK2 for cancer therapy.
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 CK2alpha 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 CK2alpha 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 CK2alpha ODN treatment, which raises the possibility of a significant therapeutic window for this therapy. Further, novel approaches such as the delivery of antisense CK2alpha 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.
Ahmad
Kashif A
KA
Cellular and Molecular Biochemistry Research Laboratory, Minneapolis Veterans Affairs Medical Center, Chaska, Minnesota 55417, USA. ahmedk@umn.edu
Wang
Guixia
G
Slaton
Joel
J
Unger
Gretchen
G
Ahmed
Khalil
K
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002214:Capsules / Q000737:chemistry / Q000627:therapeutic use; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000235:genetics; D015536:Down-Regulation; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D015398:Signal Transduction; D019063:Tenascin / Q000737:chemistry
D000970:Antineoplastic Agents; D002214:Capsules; D016376:Oligonucleotides, Antisense; D019063:Tenascin; D047390:Casein Kinase II