Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://doi.org/10.18632/oncotarget.1513 |
Resumo: | 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. |
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Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitorCasein kinase 2Chronic Lymphocytic LeukemiaCIGB-300CK2CLLSignaling therapiescigb 300creatine kinase MBpeptide derivativephosphatidylinositol 3 kinasephosphatidylinositol 3,4,5 trisphosphate 3 phosphatasephosphotransferase inhibitorunclassified drugcasein kinase IIcyclopeptideprotein kinase inhibitorPTEN protein, humanadultagedanimal experimentanimal modelanimal tissueantineoplastic activityapoptosisarticlecell proliferationcell viabilitychronic lymphatic leukemiaclinical articlecontrolled studydrug cytotoxicitydrug efficacyenzyme inhibitionfemalehumanhuman cellIC 50in vivo studyleukemia cell linemalemiddle agedmousenonhumansignal transductiontumor xenograftvery elderlyanimalantagonists and inhibitorscell growthcell survivaldrug effectsdrug screeningenzymologyLeukemia, Lymphocytic, Chronic, B-Cellmetabolismnude mouserandomizationtumor cell lineAgedAged, 80 and overAnimalsApoptosisCasein Kinase IICell Growth ProcessesCell Line, TumorCell SurvivalHumansMaleMiceMice, NudeMiddle AgedPeptides, CyclicPhosphatidylinositol 3-KinasesProtein Kinase InhibitorsPTEN PhosphohydrolaseRandom AllocationSignal TransductionXenograft Model Antitumor AssaysSDG 3 - Good Health and Well-beingWe 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.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNMartins, L.R.Perera, Y.Lúcio, P.Silva, M.G.Perea, S.E.Barata, J.T.2018-05-03T22:23:16Z2014-012014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article6application/pdfhttps://doi.org/10.18632/oncotarget.1513eng1949-2553PURE: 4076867https://www.scopus.com/inward/record.uri?eid=2-s2.0-84893861633&partnerID=40&md5=9f1d26e45d9edee74f5e9508dd933b89https://doi.org/10.18632/oncotarget.1513info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:19:32Zoai:run.unl.pt:10362/35937Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:30:23.248204Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor |
title |
Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor |
spellingShingle |
Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor Martins, L.R. 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 SDG 3 - Good Health and Well-being |
title_short |
Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor |
title_full |
Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor |
title_fullStr |
Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor |
title_full_unstemmed |
Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor |
title_sort |
Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor |
author |
Martins, L.R. |
author_facet |
Martins, L.R. Perera, Y. Lúcio, P. Silva, M.G. Perea, S.E. Barata, J.T. |
author_role |
author |
author2 |
Perera, Y. Lúcio, P. Silva, M.G. Perea, S.E. Barata, J.T. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Centro de Estudos de Doenças Crónicas (CEDOC) RUN |
dc.contributor.author.fl_str_mv |
Martins, L.R. Perera, Y. Lúcio, P. Silva, M.G. Perea, S.E. Barata, J.T. |
dc.subject.por.fl_str_mv |
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 SDG 3 - Good Health and Well-being |
topic |
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 SDG 3 - Good Health and Well-being |
description |
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. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-01 2014-01-01T00:00:00Z 2018-05-03T22:23:16Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://doi.org/10.18632/oncotarget.1513 |
url |
https://doi.org/10.18632/oncotarget.1513 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1949-2553 PURE: 4076867 https://www.scopus.com/inward/record.uri?eid=2-s2.0-84893861633&partnerID=40&md5=9f1d26e45d9edee74f5e9508dd933b89 https://doi.org/10.18632/oncotarget.1513 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
6 application/pdf |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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