Involvement of Reactive Oxygen Species in Apoptosis Induced by Pharmacological Inhibition of Protein Kinase CK2

• Published in: Annals of the New York Academy of Sciences Vol. 1171; no. 1; pp. 591 - 599
• Main Authors: Hanif, Ismail M., Ahmad, Kashif A., Ahmed, Khalil, Pervaiz, Shazib
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.08.2009
• Subjects: Apoptosis; Apoptosis - drug effects; Casein Kinase II - antagonists & inhibitors; Casein Kinase II - metabolism; Catalase; Cell Line, Tumor; CK2; Deoxyribonucleic acid; DNA Fragmentation - drug effects; Dose-Response Relationship, Drug; Flow Cytometry; Fragmentation; human leukemia cells; Humans; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Inhibition; Intracellular Space - drug effects; Intracellular Space - metabolism; Kinases; Proteins; Reactive Oxygen Species - metabolism; ROS; Superoxides - metabolism; Time Factors; Triazoles - pharmacology
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2009.04916.x

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.