Document Detail


Attenuation of breast tumor cell growth by conjugated linoleic acid via inhibition of 5-lipoxygenase activating protein.
MedLine Citation:
PMID:  16185917     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Conjugated linoleic acid (CLA) consists of a group of linoleic acid geometric isomers that have been shown to reduce tumor growth and metastasis in animal models of breast, prostate and colon cancer. To delineate a possible mechanism of action for CLA, we have recently shown that the 5-lipoxygenase product, 5-hydroxyeicosatetraenoic acid (5-HETE), could play a role in CLA alteration of mammary tumorigenesis. In this study, we determined how CLA could modulate 5-lipoxygenase activity. The t10, c12-CLA isomer reduced production of 5-HETE but not 12- and 15-HETE in MDA-MB-231 human breast tumor cells. That isomer and the c9, t11-CLA isomer decreased 5-HETE production by competition with the lipoxygenase substrate, arachidonic acid (AA). Interestingly, t10, c12-CLA reduced the expression of five-lipoxygenase activating protein (FLAP) but not the 5-lipoxygenase enzyme. Over-expression of FLAP abrogated t10, c12-CLA-reduced viability of MDA-MB-231 cells. These data suggest that the reduction of 5-HETE by t10, c12-CLA was due to competition with AA and the reduction of FLAP expression.
Authors:
Jung-Hyun Kim; Neil E Hubbard; Vincent Ziboh; Kent L Erickson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1736     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-10     Completed Date:  2005-12-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  244-50     Citation Subset:  IM    
Affiliation:
Department of Cell Biology and Human Anatomy, University of California, School of Medicine, Davis, CA 95616-8643, USA.
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MeSH Terms
Descriptor/Qualifier:
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / metabolism
Arachidonate 5-Lipoxygenase / genetics,  metabolism
Arachidonic Acid / pharmacology
Breast Neoplasms / genetics,  metabolism,  pathology
Carrier Proteins / genetics*
Cell Line, Tumor
Cell Proliferation / drug effects*
Cell Survival / drug effects,  genetics
Female
Gene Expression / drug effects
Humans
Hydroxyeicosatetraenoic Acids / metabolism,  pharmacology
Isomerism
Linoleic Acids / metabolism
Linoleic Acids, Conjugated / pharmacology*
Membrane Proteins / genetics*
Transfection
Chemical
Reg. No./Substance:
0/5-lipoxygenase-activating protein; 0/Carrier Proteins; 0/Hydroxyeicosatetraenoic Acids; 0/Linoleic Acids; 0/Linoleic Acids, Conjugated; 0/Membrane Proteins; 506-32-1/Arachidonic Acid; 5204-88-6/13-hydroxy-9,11-octadecadienoic acid; 59985-28-3/12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 72255-35-7/5-hydroxy-6,8,11,14-eicosatetraenoic acid; 73945-47-8/15-hydroxy-5,8,11,13-eicosatetraenoic acid; EC 1.13.11.34/Arachidonate 5-Lipoxygenase

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


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