Downregulation of CK2 induces apoptosis in cancer cells - A potential approach to cancer therapy

Guixia Wang, Gretchen Unger, Kashif A. Ahmad, Joel W. Slaton, Khalil Ahmed

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)77-84
Number of pages8
JournalMolecular and cellular biochemistry
Volume274
Issue number1-2
DOIs
StatePublished - Jun 2005

Bibliographical note

Funding Information:
The work was supported in part by the United States Public Health Service Research Grant UA-15062 awarded by the National Cancer Institute, Department of Health and Human Services, and in part by the Medical Research Fund of the United States Department of Veterans Affairs. We express our deep appreciation for the help provided by Alan T. Davis during the course of these experiments.

Keywords

  • Antisense
  • Apoptosis
  • CK2 inhibitors
  • Cancer
  • Nanocapsules
  • Protein kinase CK2
  • SiRNA
  • Therapy

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