| Nitric oxide induces the apoptosis of human BCR-ABL-positive myeloid leukemia cells: evidence for the chelation of intracellular iron. | |
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MedLine Citation:
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PMID: 11960353 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Anti-leukemia activity of human macrophages involves the generation of nitric oxide (NO) derivatives. However, leukemic transformation may involve mechanisms that rescue cells from NO-mediated apoptosis. In the present work, we analyzed the effects of exogenous NO on the proliferation of BCR-ABL(+) chronic myelogenous leukemia (CML) cells. As normal leukocytes, the proliferation of leukemia cells was inhibited by SNAP (S-nitroso-N-acetyl-penicillamine), GEA (Oxatriazolium amino-chloride), and SIN-1 (Morpholino-sydnonimine), whereas SNP (sodium nitroprusside) had no effect on leukemia cell growth. SIN-1 induced higher anti-proliferation activity in BCR-ABL(+) cells, compared to normal hemopoietic cells. Inhibition of leukemia cell proliferation correlated with increased apoptosis and DEVDase activity. The simultaneous addition of exogenous iron reversed NO-mediated inhibition of cell growth, caspase activation and apoptosis in all BCR-ABL(+) cells tested. The quantification of intracellular iron levels in leukemia cells indicated that NO induced an early, dose-dependent decrease in ferric iron levels. Accordingly, elevation of intracellular iron protected leukemia cells from NO-mediated apoptosis. Together, the present work reveals the presence of an iron-dependant mechanism for leukemia cell rescue from NO-induced growth inhibition and apoptosis. |
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Authors:
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H Ferry-Dumazet; M Mamani-Matsuda; M Dupouy; F Belloc; D Thiolat; G Marit; M Arock; J Reiffers; M D Mossalayi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Leukemia Volume: 16 ISSN: 0887-6924 ISO Abbreviation: Leukemia Publication Date: 2002 Apr |
Date Detail:
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Created Date: 2002-04-17 Completed Date: 2002-05-07 Revised Date: 2013-03-04 |
Medline Journal Info:
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Nlm Unique ID: 8704895 Medline TA: Leukemia Country: England |
Other Details:
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Languages: eng Pagination: 708-15 Citation Subset: IM |
Affiliation:
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Bone Marrow Transplantation, CNRS UMR5540 and EA482, Bordeaux-2 University, Bordeaux, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects*,
physiology Cell Cycle / drug effects Cell Division / drug effects Cells, Cultured / drug effects Ferricyanides / pharmacology Fusion Proteins, bcr-abl / genetics, metabolism* Humans Iron / metabolism* Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*, pathology Nitric Oxide / pharmacology* Nitric Oxide Donors / pharmacology Penicillamine / analogs & derivatives, pharmacology S-Nitroso-N-Acetylpenicillamine / pharmacology Signal Transduction / physiology |
| Chemical | |
Reg. No./Substance:
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0/Ferricyanides; 0/Fusion Proteins, bcr-abl; 0/Nitric Oxide Donors; 10102-43-9/Nitric Oxide; 52-67-5/Penicillamine; 7439-89-6/Iron; 79032-48-7/S-Nitroso-N-Acetylpenicillamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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