Involvement of reactive oxygen species in apoptosis induced by pharmacological inhibition of protein kinase CK2

Ismail M. Hanif, Kashif A. Ahmad, Khalil Ahmed, Shazib Pervaiz

Research output: Chapter in Book/Report/Conference proceedingConference contribution

15 Scopus citations

Abstract

It has been reported that inhibition of protein kinase CK2 (CK2) with antisense oligodeoxynucleotides (ODN) is a potent inducer of apoptosis in cancer cells but not in normal cells. In this regard, the apoptotic-inducing effect is attributed to the catalytic activity of the enzyme, which phosphorylates proapoptotic proteins to inhibit their functions. In this study we investigate the role of intracellular redox status in the proapoptotic activity of CK2 inhibition in human leukemia Cem cells. We provide evidence that inhibition of CK2 activity induces apoptotic cell death as evident by activation of caspase 3, DNA fragmentation, and phosphatidylserine externalization. Inhibition of CK2 resulted in a significant increase in intracellular hydrogen peroxide production, which we show as a critical mediator of apoptosis. To that end, apoptotic hallmarks, like DNA fragmentation and phosphatidylserine externalization, were blocked with the specific hydrogen peroxide scavenger catalase. We also show that inhibition of CK2 reduces cytosolic intracellular superoxide, a precursor of hydrogen peroxide. In summary, decreasing CK2 activity increases intracellular hydrogen peroxide, creating an intracellular environment conducive for death execution. Taken together, these data provide information on novel pathways involved in CK2 biology with implications for effective tools against drug-resistant tumors.

Original languageEnglish (US)
Title of host publicationNatural Compounds and Their Role in Apoptotic Cell Signaling Pathways
PublisherBlackwell Publishing Inc
Pages591-599
Number of pages9
ISBN (Print)9781573317375
DOIs
StatePublished - Aug 2009

Publication series

NameAnnals of the New York Academy of Sciences
Volume1171
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Apoptosis
  • CK2
  • Human leukemia cells
  • ROS

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