| Valproic acid, trichostatin and their combination with hemin preferentially enhance gamma-globin gene expression in human erythroid liquid cultures. | |
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MedLine Citation:
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PMID: 11454524 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND OBJECTIVES: In addition to conventional therapy, current treatment of thalassemia and sickle cell anemia includes inducers of hemoglobin F synthesis (hydroxyurea, erythropoietin, azacytidine and butyrate). However, because of concerns about the dose-limiting myelotoxicity, potential carcinogenicity and high cost of the above agents, an intensive search for less toxic or more effective drugs is ongoing. In this study we tested the effect of valproic acid and trichostatin, alone or in combination with hemin, on gamma chain synthesis in human erythroid liquid cultures. DESIGN AND METHODS: The agents were tested on erythroid human liquid cultures derived from normal peripheral blood, peripheral blood from beta(s)/beta(thal) patients, normal cord blood and normal bone marrow samples. The effect of the agents was expressed as increase of gamma/gamma+beta m-RNA, measured with competitive reverse transcriptase-polymerase chain recation (RT-PCR), or as increase of HbF, measured by high performance liquid chromatography (HPLC). RESULTS: Addition of valproic acid or trichostatin to human erythroid cell cultures preferentially enhanced gamma mRNA synthesis in all blood samples (2.9 to 3.5-fold). The addition of hemin enhanced the effect up to 10-fold. INTERPRETATION AND CONCLUSIONS: Valproic acid, trichostatin and their combination with hemin (all three FDA-approved drugs) preferentially increase gamma-globin chain synthesis and may be helpful for the treatment of hemoglobinopathies. |
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Authors:
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P Marianna; P Kollia; S Akel; Y Papassotiriou; A Stamoulakatou; D Loukopoulos |
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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: Haematologica Volume: 86 ISSN: 0390-6078 ISO Abbreviation: Haematologica Publication Date: 2001 Jul |
Date Detail:
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Created Date: 2001-07-16 Completed Date: 2002-01-02 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0417435 Medline TA: Haematologica Country: Italy |
Other Details:
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Languages: eng Pagination: 700-5 Citation Subset: IM |
Affiliation:
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First Department of Medicine, University of Athens, Laikon Hospital, Greece. dloukop@otenet.gr |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antifungal Agents
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pharmacology Cells, Cultured / drug effects Drug Interactions Erythroid Precursor Cells / cytology, drug effects, metabolism GABA Agents / pharmacology Gene Expression / genetics Globins / drug effects*, genetics Hemin / pharmacology* Humans Hydroxamic Acids / pharmacology* Valproic Acid / pharmacology* beta-Thalassemia / pathology |
| Chemical | |
Reg. No./Substance:
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0/Antifungal Agents; 0/GABA Agents; 0/Hydroxamic Acids; 16009-13-5/Hemin; 58880-19-6/trichostatin A; 9004-22-2/Globins; 99-66-1/Valproic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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