Abstract
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 PI3Kmediated 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.
Original language | English |
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Pages (from-to) | 258-263 |
Number of pages | 6 |
Journal | Oncotarget |
Volume | 5 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jan 2014 |
Keywords
- Casein kinase 2
- Chronic Lymphocytic Leukemia
- CIGB-300
- CK2
- CLL
- Signaling therapies
- cigb 300
- creatine kinase MB
- peptide derivative
- phosphatidylinositol 3 kinase
- phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase
- phosphotransferase inhibitor
- unclassified drug
- casein kinase II
- cyclopeptide
- protein kinase inhibitor
- PTEN protein, human
- adult
- aged
- animal experiment
- animal model
- animal tissue
- antineoplastic activity
- apoptosis
- article
- cell proliferation
- cell viability
- chronic lymphatic leukemia
- clinical article
- controlled study
- drug cytotoxicity
- drug efficacy
- enzyme inhibition
- female
- human
- human cell
- IC 50
- in vivo study
- leukemia cell line
- male
- middle aged
- mouse
- nonhuman
- signal transduction
- tumor xenograft
- very elderly
- animal
- antagonists and inhibitors
- cell growth
- cell survival
- drug effects
- drug screening
- enzymology
- Leukemia, Lymphocytic, Chronic, B-Cell
- metabolism
- nude mouse
- randomization
- tumor cell line
- Aged
- Aged, 80 and over
- Animals
- Apoptosis
- Casein Kinase II
- Cell Growth Processes
- Cell Line, Tumor
- Cell Survival
- Humans
- Male
- Mice
- Mice, Nude
- Middle Aged
- Peptides, Cyclic
- Phosphatidylinositol 3-Kinases
- Protein Kinase Inhibitors
- PTEN Phosphohydrolase
- Random Allocation
- Signal Transduction
- Xenograft Model Antitumor Assays