دورية أكاديمية
Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor
| العنوان: | Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor |
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| المؤلفون: | Martins, L.R., Perera, Y., Lúcio, P., Silva, M.G., Perea, S.E., Barata, J.T. |
| المساهمون: | Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) |
| سنة النشر: | 2014 |
| المجموعة: | Repositório da Universidade Nova de Lisboa (UNL) |
| مصطلحات موضوعية: | 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 |
| الوصف: | We are grateful to all the patients that contributed to this study. We thank Dr. Riccardo Dalla-Favera for providing the MO1043 cell line and Dr. John Byrd for providing the WaC3CD5 cell line. We also thank the Helena Alaiz and Teresa Faria (Cytogenetics and Flow Cytometry sections of the Hemato-oncology lab at Instituto Portugues de Oncologia) for the cytogenetic and phenotypic characterization, respectively, of patient samples. This work was supported by the grant PIC/IC/83193/2007 from Fundacao para a Ciencia e a Tecnologia. LRM received an FCT-SFRH PhD fellowship. ; 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. ; publishersversion ; published |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1949-2553 |
| العلاقة: | info:eu-repo/grantAgreement/FCT/5646-ICCMS/83193/PT; PURE: 4076867; PURE UUID: 82017eaf-69d9-43fe-b951-31b0e5323169; RIS: urn:84888E3E2C3C10BFE8DC6ECA5AD0891C; PubMed: 24473900; WOS: 000332698000026; Scopus: 84893861633; https://www.scopus.com/inward/record.uri?eid=2-s2.0-84893861633&partnerID=40&md5=9f1d26e45d9edee74f5e9508dd933b89Test; https://doi.org/10.18632/oncotarget.1513Test |
| DOI: | 10.18632/oncotarget.1513 |
| الإتاحة: | https://doi.org/10.18632/oncotarget.1513Test https://www.scopus.com/inward/record.uri?eid=2-s2.0-84893861633&partnerID=40&md5=9f1d26e45d9edee74f5e9508dd933b89Test |
| حقوق: | openAccess |
| رقم الانضمام: | edsbas.F4E9375D |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19492553 |
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| DOI: | 10.18632/oncotarget.1513 |