Research Papers:
Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor
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Abstract
Leila R. Martins1, Yasser Perera2, Paulo Lúcio3, Maria G. Silva3, Silvio E. Perea2, João T. Barata1
1 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal;
2 Centro de Ingeniería Genética y Biotecnología, Havana, Cuba;
3 CEDOC, Faculdade de Ciências Médicas, FCM, Universidade Nova de Lisboa and Instituto Português de Oncologia, Lisbon, Portugal.
Correspondence:
João T. Barata, email:
Keywords: Chronic Lymphocytic Leukemia, CLL, Casein kinase 2, CK2, CIGB-300, Signaling therapies.
Received: October 17, 2013 Accepted: December 11, 2013 Published: December 13, 2013
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 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.
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