Document Detail


Arsenic-trioxide-induced apoptosis of chronic lymphocytic leukemia cells.
MedLine Citation:
PMID:  19208092     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic lymphocytic leukemia (CLL) cells are characterized by defective apoptosis which leads to their extended survival. Arsenic trioxide (As(2)O(3)) was reported to induce cell death in many malignant cells, but the specific pathway of As(2)O(3)-induced apoptosis/necrosis remains controversial. Our aim was to determine if As(2)O(3) kills CLL cells through apoptosis and whether this is accompanied by reduction in Bcl-2 levels. Cells from nine patients with CLL were incubated with increasing concentrations of As(2)O(3) (0.5-2 microM) for 2, 7, or 14 days. Cells viability was measured using Alamar Blue assay and apoptosis using human Annexin V-FITC and propidium iodine (PI) kit (BMS306FI; Bender MedSystems, Vienna, Austria). Intracellular Bcl-2, Bax, and caspase-3 levels were measured by flow cytometry. As(2)O(3) significantly reduced CLL cell viability (P < 0.01) and induced apoptotic cell death in a time- and dose-dependent manner. After 7 days, CLL cells showed a significant decrease in mean fluorescence intensity (MFI) of Bcl-2 on flow cytometry study. Bax and caspase-3 levels showed significant decrease in MFI only after prolonged incubations (7 and 14 days) and mostly at higher concentrations of As(2)O(3). The mechanism underlying the reduction in viability of CLL cells incubated with As(2)O(3) is mediated by induction of apoptosis maybe through the down-regulation of Bcl-2. Further studies are needed to elucidate the potential therapeutic role of As(2)O(3) in CLL.
Authors:
O Bairey; A Vanichkin; O Shpilberg
Publication Detail:
Type:  Journal Article     Date:  2009-02-05
Journal Detail:
Title:  International journal of laboratory hematology     Volume:  32     ISSN:  1751-553X     ISO Abbreviation:  Int J Lab Hematol     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-21     Completed Date:  2010-04-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101300213     Medline TA:  Int J Lab Hematol     Country:  England    
Other Details:
Languages:  eng     Pagination:  e77-85     Citation Subset:  IM    
Affiliation:
Institute of Hematology, Rabin Medical Center, Beilinson Hospital, Petah Tiqwa, Israel. obairey@post.tau.ac.il
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Arsenicals / pharmacology*
Cell Survival / drug effects
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy,  pathology*
Male
Oxides / pharmacology*
Proto-Oncogene Proteins c-bcl-2 / metabolism
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Arsenicals; 0/Oxides; 0/Proto-Oncogene Proteins c-bcl-2; 1327-53-3/arsenic trioxide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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