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

• 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

抄録

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.

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Leukemia, 25(4), pp.575-578; 2011

収録刊行物

• Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K

  Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 25 (4), 575-578, 2011-04

  Nature Publishing Group

キーワード

• Oncology
• Cancer Research
• Hematology

詳細情報

• CRID: 1050005822297954432
• NII論文ID: 120006984803
• NII書誌ID: AA10668706
• ISSN: 08876924
• ISSN: 14765551
• DOI: 10.1038/leu.2010.315
• HANDLE: 10069/24828
• Web Site: https://nagasaki-u.repo.nii.ac.jp/records/14825
• Web Site: http://www.nature.com/articles/leu2010315.pdf
• Web Site: http://www.nature.com/articles/leu2010315
• 本文言語コード: en
• 資料種別: journal article
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