15 275

Cited 28 times in

Histone deacetylase inhibitors synergistically potentiate death receptor 4-mediated apoptotic cell death of human T-cell acute lymphoblastic leukemia cells.

Authors
Sung, ES; Kim, A; Park, JS; Chung, J; Kwon, MH; Kim, YS
Citation
Apoptosis : an international journal on programmed cell death, 15(10):1256-1269, 2010
Journal Title
Apoptosis : an international journal on programmed cell death
ISSN
1360-81851573-675X
Abstract
Cell-death signaling through the pro-apoptotic tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptors, death receptor 4 (DR4) and DR5, has shown tumor-selective apoptotic activity. Here, we examine susceptibility of various leukemia cell lines (HL-60, U937, K562, CCRF-CEM, CEM-CM3, and THP-1) to an anti-DR4 agonistic monoclonal antibody (mAb), AY4, in comparison with TRAIL. While most of the leukemia cell lines were intrinsically resistant to AY4 or TRAIL alone, the two T-cell acute lymphoblastic leukemia (T-ALL) lines, CEM-CM3 and CCRF-CEM cells, underwent synergistic caspase-dependent apoptotic cell death by combination of AY4 or TRAIL with a histone deacetylase inhibitor (HDACI), either suberoylanilide hydroxamic acid (SAHA) or valproic acid (VPA). All of the combined treatments synergistically downregulated several anti-apoptotic proteins (c-FLIP, Bcl-2, Bcl-X(L), XIAP, and survivin) without significant changing the expression levels of pro-apoptotic proteins (Bax and Bak) or the receptors (DR4 and DR5). Downregulation of c-FLIP to activate caspase-8 was a critical step for the synergistic apoptosis through both extrinsic and intrinsic apoptotic pathways. Our results demonstrate that the HDACIs have synergistic effects on DR4-specific mAb AY4-mediated cell death in the T-ALL cells with comparable competence to those exerted by TRAIL, providing a new strategy for the targeted treatment of human T-ALL cells.
MeSH terms
Antibodies, Monoclonal/pharmacologyAntineoplastic Agents/pharmacologyApoptosis/*drug effectsBlotting, WesternCaspases/metabolismCell Line, TumorDown-RegulationDrug SynergismFlow CytometryHistone Deacetylase Inhibitors/*pharmacologyHistone Deacetylases/metabolismHumansHydroxamic Acids/*pharmacologyInhibitor of Apoptosis Proteins/metabolismMitochondria/drug effects/metabolismPrecursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism/*pathologyRNA, Small InterferingReceptors, Tumor Necrosis Factor/*immunology/*metabolismSignal Transduction/drug effectsTNF-Related Apoptosis-Inducing Ligand/metabolism/pharmacologyValproic Acid/*pharmacology
DOI
10.1007/s10495-010-0521-9
PMID
20582477
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Hematology-Oncology
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
박준성권명희
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse