Inhibition of protein kinase CK2 expression and activity blocks tumor cell growth.
Protein kinase CK2 (CK2) is a highly conserved and ubiquitous serine/threonine kinase. It is a multifunctional and pleiotropic protein kinase implicated in the regulation of cell proliferation, survival, and differentiation. Deregulation of CK2 is observed in a wide variety of tumors. It has been the focus of intensive research efforts to establish the cause-effect relationship between CK2 and neoplastic growth. Here, we further validate the role of CK2 in cancer cell growth using siRNA approach. We also screened a library of more than 200,000 compounds and identified several molecules, which inhibit CK2 with IC(50) < 1 microM. The binding mode of a representative compound with maize CK2 was determined. In addition, the cellular activity of the compounds was demonstrated by their inhibition of phosphorylation of PTEN Ser370 in HCT116 cells. Treatment of a variety of cancer cell lines with the newly identified CK2 inhibitor significantly blocked cell growth with IC(50)s as low as 300 nM.
Zhu
Dan
D
Celgene Corporation, 4550 Towne Centre Court, San Diego, CA 92121, USA. dzhu@celgene.com
Hensel
Jennifer
J
Hilgraf
Robert
R
Abbasian
Mahan
M
Pornillos
Owen
O
Deyanat-Yazdi
Gordafaried
G
Hua
Xuequn Helen
XH
Cox
Sarah
S
D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D009363:Neoplasm Proteins; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000494:pharmacology; D054852:Small Molecule Libraries
D004791:Enzyme Inhibitors; D008024:Ligands; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D054852:Small Molecule Libraries; D047390:Casein Kinase II; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human