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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.
- Source :
-
Leukemia (08876924) . Apr2011, Vol. 25 Issue 4, p575-587. 13p. 1 Black and White Photograph, 1 Chart, 6 Graphs. - Publication Year :
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *LEUKEMIA
*LYMPHOMAS
*APOPTOSIS
*TUMORS
*CELL proliferation
Subjects
Details
- Language :
- English
- ISSN :
- 08876924
- Volume :
- 25
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Leukemia (08876924)
- Publication Type :
- Academic Journal
- Accession number :
- 59962924
- Full Text :
- https://doi.org/10.1038/leu.2010.315