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Gallic acid downregulates matrix metalloproteinase-2 (MMP-2) and MMP-9 in human leukemia cells with expressed Bcr/Abl.
MedLine Citation:
PMID:  22865631     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Ying-Jung Chen; Long-Sen Chang
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-3
Journal Detail:
Title:  Molecular nutrition & food research     Volume:  -     ISSN:  1613-4133     ISO Abbreviation:  Mol Nutr Food Res     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101231818     Medline TA:  Mol Nutr Food Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
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