Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor.
Chronic lymphocytic leukemia (CLL) remains an incurable malignancy, urging for the identification of new molecular targets for therapeutic intervention. CLL cells rely on overexpression and hyperactivation of the ubiquitous serine/threonine protein kinase CK2 for their viability in vitro. CIGB-300 is a cell-permeable selective CK2 inhibitor peptide undergoing clinical trials for several cancers. Here, we show that CIGB-300 promotes activation of the tumor suppressor PTEN and abrogates PI3K-mediated downstream signaling in CLL cells. In accordance, CIGB-300 decreases the viability and proliferation of CLL cell lines, promotes apoptosis of primary leukemia cells and displays antitumor efficacy in a xenograft mouse model of human CLL. Our studies provide pre-clinical support for the testing and possible inclusion of CK2 inhibitors in the clinical arsenal against CLL.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Leila R
LR
Martins
Yasser
Y
Perera
Paulo
P
Lúcio
Maria G
MG
Silva
Silvio E
SE
Perea
João T
JT
Barata
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D051059:PTEN Phosphohydrolase; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D047390:Casein Kinase II; D051059:PTEN Phosphohydrolase; D010456:Peptides, Cyclic; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; C494929:PTEN protein, human; C532510:CIGB-300