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LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway.

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Title: LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway.
Authors: Hasegawa, H / Yamada, Yasuaki / Tsukasaki, Katsumi / Mori, N / Tsuruda, Kazuto / Sasaki, Daisuke / Usui, Tetsuya / Osaka, Akemi / Atogami, Sunao / Ishikawa, Chie / Machijima, Yoshiaki / Sawada, S / Hayashi, Tomayoshi / Miyazaki, Yasushi / Kamihira, Shimera
Issue Date: Apr-2011
Publisher: Nature Publishing Group
Citation: Leukemia, 25(4), pp.575-578; 2011
Abstract: Adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm etiologically associated with human T-lymphotropic virus type-1 (HTLV-1), is resistant to treatment. In this study, we examined the effects of a new inhibitor of deacetylase enzymes, LBH589, on ATLL cells. LBH589 effectively induced apoptosis in ATLL-related cell lines and primary ATLL cells and reduced the size of tumors inoculated in SCID mice. Analyses, including with a DNA microarray, revealed that neither death receptors nor p53 pathways contributed to the apoptosis. Instead, LBH589 activated an intrinsic pathway through the activation of caspase-2. Furthermore, small interfering RNA experiments targeting caspase-2, caspase-9, RAIDD, p53-induced protein with a death domain (PIDD) and RIPK1 (RIP) indicated that activation of RAIDD is crucial and an event initiating this pathway. In addition, LBH589 caused a marked decrease in levels of factors involved in ATLL cell proliferation and invasion such as CCR4, IL-2R and HTLV-1 HBZ-SI, a spliced form of the HTLV-1 basic zipper factor HBZ. In conclusion, we showed that LBH589 is a strong inducer of apoptosis in ATLL cells and uncovered a novel apoptotic pathway initiated by activation of RAIDD.Leukemia advance online publication, 18 January 2011; doi:10.1038/leu.2010.315.
Description: This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
URI: http://hdl.handle.net/10069/24828
ISSN: 08876924
DOI: 10.1038/leu.2010.315
PubMed ID: 21242994
Rights: © 2011 Macmillan Publishers Limited All rights reserved 0887-6924/11
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/24828

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