Source:http://linkedlifedata.com/resource/pubmed/id/21349264
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2011-3-22
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pubmed:abstractText |
Mycophenolic acid (MPA) has been known for decades to be an anticancer and immunosuppressive agent and has significant anticancer properties, but its underlying molecular mechanisms are poorly characterized. Peroxisome proliferator-activated receptor gamma (PPAR?) has a central role in adipocyte differentiation, and MPA has been shown to be a potent PPAR? agonist. Whether PPAR? activation has a putative role in the anticancer efficacy of MPA via induction of adipocyte-like differentiation has not been elucidated. In the present study, MPA was demonstrated to dose-dependently activate PPAR? transcription in the GAL4-hPPAR? (LBD) chimeric receptor assay and PPRE-luc reporter gene assay with an EC(50) of 5.2-9.3 ?M. Treatment of the breast cancer cell lines MDA-MB-231 and MCF-7 with MPA resulted in differentiation of adipose tissue that was characterized by accumulation of intracellular lipids, enlargement of cell volume, and permanent withdrawal from the cell cycle at the G1/G0 stage. At a molecular level, the expression of three adipocyte differentiation markers (PPAR?, adipsin D, and aP2) was remarkably induced in differentiated breast cancer cells. However, RNA interference experiments showed that PPAR?-knockdown cannot completely reverse the differentiated state of MDA-MB-231 cells after MPA treatment. These data suggest that the effects of MPA on adipocyte-like terminal differentiation of breast cancer cells are (at least in part) due to PPAR? activation, which is a novel anticancer mechanism of MPA.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1879-0712
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pubmed:author | |
pubmed:copyrightInfo |
Copyright © 2011 Elsevier B.V. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
658
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-8
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pubmed:meshHeading |
pubmed-meshheading:21349264-Adipocytes,
pubmed-meshheading:21349264-Animals,
pubmed-meshheading:21349264-Antineoplastic Agents,
pubmed-meshheading:21349264-Breast Neoplasms,
pubmed-meshheading:21349264-CHO Cells,
pubmed-meshheading:21349264-Cell Differentiation,
pubmed-meshheading:21349264-Cell Line, Tumor,
pubmed-meshheading:21349264-Cell Proliferation,
pubmed-meshheading:21349264-Cricetinae,
pubmed-meshheading:21349264-Cricetulus,
pubmed-meshheading:21349264-G0 Phase,
pubmed-meshheading:21349264-G1 Phase,
pubmed-meshheading:21349264-Gene Knockdown Techniques,
pubmed-meshheading:21349264-Humans,
pubmed-meshheading:21349264-Mycophenolic Acid,
pubmed-meshheading:21349264-PPAR gamma,
pubmed-meshheading:21349264-Transcription, Genetic
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pubmed:year |
2011
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pubmed:articleTitle |
Mycophenolic acid induces adipocyte-like differentiation and reversal of malignancy of breast cancer cells partly through PPAR?.
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pubmed:affiliation |
College of Life Science, Hebei Normal University, Shijiazhuang, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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