Casein kinase II inhibition induces apoptosis in pancreatic cancer cells.
Pancreatic cancer is one of the most common causes of cancer death in western civilization. The five-year survival rate is below 1% and of the 10% of patients with resectable disease only around one-fifth survives 5 years. Survival rates have not changed much during the last 20 years, demonstrating the inefficacy of current available therapies. To improve the prognosis of pancreatic cancer, there is the need to develop effective non-surgical treatment for this disease. The protein kinase casein kinase II (CK2) is a ubiquitously expressed serine-threonine kinase and its activity is enhanced in all human tumors examined so far. The contribution of CK2 to the tumor maintenance of pancreatic cancer has not been investigated. To investigate the function of CK2 in pancreatic cancer cells we used the CK2 specific inhibitors 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole and Apigenin. Furthermore, we interfered with CK2 expression using CK2 specific siRNAs. Interfering with CK2 function led to a reduction of pancreatic cancer cell viability, which was due to caspase-dependent apoptosis. The induction of apoptosis correlated with a reduced NF-kappaB-dependent transcriptional activity. This study validates CK2 as a molecular drug target in a preclinical in vitro model of pancreatic cancer.
Second Department of Internal Medicine, Technical University of Munich, Germany.
Rainer
R
Hamacher
Dieter
D
Saur
Ralph
R
Fritsch
Maximilian
M
Reichert
Roland M
RM
Schmid
Günter
G
Schneider
D017209:Apoptosis / Q000502:physiology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D002470:Cell Survival; D006801:Humans; D009838:Oligodeoxyribonucleotides; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D009838:Oligodeoxyribonucleotides; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D047390:Casein Kinase II