In:
Cancer Science, Wiley, Vol. 107, No. 8 ( 2016-08), p. 1124-1133
Abstract:
Adult T‐cell leukemia/lymphoma ( ATL ) is an aggressive T‐cell malignancy caused by human T‐cell lymphotropic virus 1. Treatment options for acute ATL patients include chemotherapy, stem cell transplantation, and recently the anti‐chemokine (C‐C motif) receptor 4 antibody, although most patients still have a poor prognosis and there is a clear need for additional options. HBI ‐8000 is a novel oral histone deacetylase inhibitor with proven efficacy for treatment of T‐cell lymphomas that recently received approval in China. In the present study, we evaluated the effects of HBI ‐8000 on ATL ‐derived cell lines and primary cells obtained from Japanese ATL patients. In most cases HBI ‐8000 induced apoptosis in both primary ATL cells and cell lines. In addition, findings obtained with DNA microarray suggested Bim activation and, interestingly, the contribution of the NLR family, pyrin domain containing 3 ( NLRP 3) inflammasome pathway in HBI ‐8000‐induced ATL cell death. Further investigations using si RNA s confirmed that Bim contributes to HBI ‐8000‐induced apoptosis. Our results provide a rationale for a clinical investigation of the efficacy of HBI ‐8000 in patients with ATL . Although the role of NLRP 3 inflammasome activation in ATL cell death remains to be verified, HBI ‐8000 may be part of a novel therapeutic strategy for cancer based on the NLRP 3 pathway.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2016.107.issue-8
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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