| Gallic acid downregulates matrix metalloproteinase-2 (MMP-2) and MMP-9 in human leukemia cells with expressed Bcr/Abl. | |
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MedLine Citation:
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PMID: 22865631 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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SCOPE: The aim of the present study was to explore the signaling pathways associated with gallic acid induced matrix metalloproteinase-2 (MMP-2)/MMP-9 downregulation in human leukemia K562 cells. METHODS AND RESULTS: Unlike the insignificant effect on human Bcr/Abl-negative leukemia U937 cells, gallic acid attenuated invasion of human Bcr/Abl-positive leukemia K562 cells with characteristic of decreased protein expression and mRNA levels of MMP-2 and MMP-9. Gallic acid induced β-TrCP upregulation evoked Bcr/Abl degradation in K562 cells, while overexpression of Bcr/Abl attenuated gallic acid induced MMP-2/MMP-9 downregulation. Overexpression of Bcr/Abl restored the levels of phospho-ERK and phospho-Akt but not JNK phosphorylation in gallic acid treated K562 cells. Gallic acid treatment repressed Akt/ERK-mediated c-Fos phosphorylation and JNK1-mediated ATF-2 phosphorylation. c-Jun inactivation was mediated through gallic acid induced Akt/ERK and JNK inactivation. Knockdown of c-Fos, c-Jun, and ATF-2 by siRNA and luciferase promoter assay reflected that c-Jun/ATF-2 and c-Jun/c-Fos were, respectively, responsible for MMP-2 and MMP-9 expression in K562 cells. Chromatin immunoprecipitating assay showed that gallic acid reduced the binding of c-Jun/ATF-2 and c-Jun/c-Fos with promoter region of MMP-2 and MMP-9 genes, respectively. CONCLUSION: Our data indicate that MMP-2 and MMP-9 downregulation in gallic acid treated K562 cells are mediated through suppression of JNK1-mediated c-Jun/ATF-2 and Akt/ERK-mediated c-Jun/c-Fos pathways, respectively. |
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Authors:
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Ying-Jung Chen; Long-Sen Chang |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-8-3 |
Journal Detail:
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Title: Molecular nutrition & food research Volume: - ISSN: 1613-4133 ISO Abbreviation: Mol Nutr Food Res Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-8-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101231818 Medline TA: Mol Nutr Food Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
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Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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