Document Detail


Polyunsaturated fatty acids inhibit PI3K activity in a yeast-based model system.
MedLine Citation:
PMID:  19557793     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The phosphatidylinositol 3-kinase (PI3K) pathway controls the regulation of cell growth, proliferation, migration and apoptosis. In many tumors, the PI3K gene is mutated or overexpressed, and/or the PI3K pathway is hyperactive. PI3K is therefore a potential pharmacological target for the development of anti-tumor drugs. Some polyunsaturated fatty acids (PUFA), when given in the diet, may lead to a decrease in PI3K activity. We used a yeast-based model to reconstitute the PI3K/PTEN/Akt pathway to study the effects of long-chain polyunsaturated n-3 fatty acids on PI3K, and found that various PUFA were able to alleviate toxicity induced by overexpression of PI3K. The various PUFA had no significant effect on the steady-state level of PI3K catalytic subunit proteins (p110alpha) in yeast. However, depletion of phosphatidylinositol 4,5-bisphosphate due to overexpression of the p110alpha subunit was significantly reduced by treating the yeast cells with the various PUFA. The inhibition of mammalian PI3K, expressed in an exogenous cellular context in yeast, is likely to be a direct effect of these PUFA on PI3K rather than on other mammalian endogenous or environmental factors. These results are particularly promising given the abundance of active PUFA in marine foodstuffs and especially fish oils.
Authors:
Elodie Couplan; Marie Le Cann; Christelle Le Foll; Charlotte Corporeau; Marc Blondel; Jacques Delarue
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biotechnology journal     Volume:  4     ISSN:  1860-7314     ISO Abbreviation:  Biotechnol J     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-19     Completed Date:  2009-11-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101265833     Medline TA:  Biotechnol J     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1190-7     Citation Subset:  IM    
Affiliation:
INSERM U, Brest, France.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors*,  metabolism*
Animals
Antineoplastic Agents / pharmacology
Arachidonic Acids / chemistry
Catalytic Domain
Enzyme Inhibitors / pharmacology
Fatty Acids, Unsaturated / chemistry,  pharmacology*
Gene Expression Regulation, Enzymologic*
Glucose / metabolism
Humans
Mutation
Neoplasms / drug therapy,  pathology
Nutritional Sciences
Plasmids / metabolism
Saccharomyces cerevisiae / metabolism
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Arachidonic Acids; 0/Enzyme Inhibitors; 0/Fatty Acids, Unsaturated; 50-99-7/Glucose; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase

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