Document Detail


Histone deacetylase inhibitors induce growth arrest and apoptosis of HTLV-1-infected T-cells via blockade of signaling by nuclear factor kappaB.
MedLine Citation:
PMID:  17644177     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive disease with a poor prognosis in which nuclear factor kappa B (NF-kappaB) is thought to play a role. This study explored the effects of histone deacetylase inhibitors (HDACIs) MS-275, suberoylanilide hydroxamic acid (SAHA), and LBH589 on both human T-cell lymphotropic virus type I (HTLV-1)-infected T cells (MT-1, -2, -4, and HUT102) and freshly isolated ATL cells harvested from patients. HDACIs effectively inhibited the proliferation of these cells. For example, MS-275, SAHA, and LBH589 effectively inhibited the proliferation of MT-1 cells with ED(50s) of 6microM, 2.5microM, and 100nM, respectively, as measured by 3-(4,5-dimethylithiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay on day 2 of culture. In addition, HDACIs induced cell cycle arrest at the G2/M phase and apoptosis of HTLV-1-infected T-cells in conjunction with regulation of apoptosis-related proteins. Electrophoretic mobility shift assay showed that exposure of HTLV-1-infected T-cells to HDACIs for 48h inhibited formation of the NF-kappaB/DNA binding complex. Moreover, we found that HDACIs accumulated NF-kappaB and inhibitory subunit of NF-kappaB in the cytoplasm in conjunction with the down-regulation of NF-kappaB in the nucleus, suggesting that HDACIs blocked nuclear translocation of NF-kappaB. Based on these findings, we believe HDACIs can be useful for treating patients with ATL or other types of cancer in which NF-kappaB plays a role.
Authors:
Chie Nishioka; Takayuki Ikezoe; Jing Yang; Naoki Komatsu; Kentaro Bandobashi; Ayuko Taniguchi; Yoshio Kuwayama; Kazuto Togitani; H Phillip Koeffler; Hirokuni Taguchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-20
Journal Detail:
Title:  Leukemia research     Volume:  32     ISSN:  0145-2126     ISO Abbreviation:  Leuk. Res.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-15     Completed Date:  2008-05-20     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7706787     Medline TA:  Leuk Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  287-96     Citation Subset:  IM    
Affiliation:
Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology
Apoptosis / drug effects*
Benzamides / pharmacology
Blotting, Western
Cell Line
Cell Proliferation / drug effects*
Deltaretrovirus Infections / drug therapy
Electrophoretic Mobility Shift Assay
Enzyme Inhibitors / pharmacology*
Flow Cytometry
Histone Deacetylase Inhibitors
Human T-lymphotropic virus 1
Humans
Hydroxamic Acids / pharmacology
Immunohistochemistry
Leukemia-Lymphoma, Adult T-Cell / drug therapy*
NF-kappa B / drug effects*
Pyridines / pharmacology
Signal Transduction / drug effects
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Benzamides; 0/Enzyme Inhibitors; 0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/LBH589; 0/N-(2-aminophenyl)-4-(N-(pyridin-3-ylmethoxycarbonyl)aminomethyl)benzamide; 0/NF-kappa B; 0/Pyridines; 149647-78-9/vorinostat

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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