| Arsenic-trioxide-induced apoptosis of chronic lymphocytic leukemia cells. | |
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MedLine Citation:
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PMID: 19208092 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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O Bairey; A Vanichkin; O Shpilberg |
Publication Detail:
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Type: Journal Article Date: 2009-02-05 |
Journal Detail:
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Title: International journal of laboratory hematology Volume: 32 ISSN: 1751-553X ISO Abbreviation: Int J Lab Hematol Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-21 Completed Date: 2010-04-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101300213 Medline TA: Int J Lab Hematol Country: England |
Other Details:
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Languages: eng Pagination: e77-85 Citation Subset: IM |
Affiliation:
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Institute of Hematology, Rabin Medical Center, Beilinson Hospital, Petah Tiqwa, Israel. obairey@post.tau.ac.il |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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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:
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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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