Document Detail


Resveratrol-mediated reversal of doxorubicin resistance in acute myeloid leukemia cells via downregulation of MRP1 expression.
MedLine Citation:
PMID:  20350534     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chemo-resistance to anti-cancer drugs is a major obstacle in efforts to develop a successful treatment of acute myeloid leukemia (AML). In this study, we investigate whether resveratrol, a common ingredient in a broad variety of fruits and vegetables, can reverse drug resistance in AML cells. Three doxorubicin-resistant AML cell lines (AML-2/DX30, AML-2/DX100, AML-2/DX300) were prepared via long-term exposure to doxorubicin for more than 3 months. DNA microarray analysis demonstrated that many genes were differentially expressed in the resistant cells, as compared with the wild type AML-2/WT cells. In particular, the expression level of the MRP1 gene was significantly increased in the AML-2/DX300 cells, as compared to that detected in AML-2 cells. Importantly, the resveratrol was shown not only to induce cell growth arrest and apoptotic death in doxorubicin-resistant AML cells, but was also shown to downregulate the expression of an MRP1 gene. Furthermore, resveratrol treatment induced a significant increase in the uptake of 5(6)-carboxyfluorescein diacetate, a MRP1 substrate, into the doxorubicin-resistant AML-2/DX300 cells. The results of this study show that resveratrol may facilitate the cellular uptake of doxorubicin via an induced downregulation of MRP1 expression, and also suggest that it may prove useful in overcoming doxorubicin resistance, or in sensitizing doxorubicin-resistant AML cells to anti-leukemic agents.
Authors:
Sin Ho Kweon; Ju Han Song; Tae Sung Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-27
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  395     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-26     Completed Date:  2010-05-07     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  104-10     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Inc. All rights reserved.
Affiliation:
Division of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / genetics
Cell Line, Tumor
Cell Proliferation / drug effects
Down-Regulation
Doxorubicin / metabolism*,  pharmacology,  therapeutic use
Drug Resistance, Neoplasm / drug effects*,  genetics
Fluoresceins / metabolism
Gene Expression / drug effects
Humans
Leukemia, Myeloid, Acute / drug therapy*,  metabolism
Multidrug Resistance-Associated Proteins / genetics*,  metabolism
Oligonucleotide Array Sequence Analysis
Stilbenes / pharmacology*
Chemical
Reg. No./Substance:
0/Fluoresceins; 0/Multidrug Resistance-Associated Proteins; 0/Stilbenes; 0/multidrug resistance-associated protein 1; 23214-92-8/Doxorubicin; 3301-79-9/6-carboxyfluorescein; Q369O8926L/resveratrol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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