Document Detail


Omega-3 fatty acid inhibition of prostate cancer progression to hormone independence is associated with suppression of mTOR signaling and androgen receptor expression.
MedLine Citation:
PMID:  21667400     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Currently, progression of prostate cancer to androgen independence remains the primary obstacle to improved survival. In order to improve overall survival, novel treatment strategies that are based upon specific molecular mechanisms that prolong the androgen-dependent state and that are useful for androgen-independent disease need to be identified. Both epidemiological as well as preclinical data suggest that omega-3 fatty acids are effective primary tumor prevention agents; however, their efficacy at preventing and treating refractory prostate cancer has not been as thoroughly investigated. We used an in vitro model of androgen ablation to determine the effect of treatment with omega-3 fatty acids on the progression to an androgen-independent state. The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were able to prevent progression of LNCaP cells while the omega-6 fatty acid arachidonic acid (AA) actually promoted cell growth under conditions of hormone depletion. These results correlated with a decrease in the expression of the androgen receptor as well as suppression of the Akt/mTOR signaling pathway. Connecting the mechanisms by which omega-3 fatty acids affect phenotypic outcome is important for effective exploitation of these nutrient agents as a therapeutic approach. Understanding these processes is critical for the development of effective dietary intervention strategies that improve overall survival.
Authors:
William Friedrichs; Shivani B Ruparel; Robert A Marciniak; Linda deGraffenried
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2011-06-11
Journal Detail:
Title:  Nutrition and cancer     Volume:  63     ISSN:  1532-7914     ISO Abbreviation:  Nutr Cancer     Publication Date:  2011  
Date Detail:
Created Date:  2011-07-19     Completed Date:  2011-12-12     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  7905040     Medline TA:  Nutr Cancer     Country:  England    
Other Details:
Languages:  eng     Pagination:  771-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Androgens / metabolism*
Cell Line, Tumor
Cell Proliferation
Clone Cells
Docosahexaenoic Acids / metabolism
Eicosapentaenoic Acid / metabolism
Fatty Acids, Omega-3 / metabolism*
Humans
Male
Neoplasm Proteins / metabolism*
Phosphorylation
Prostatic Neoplasms / diet therapy,  metabolism*
Protein Processing, Post-Translational
Proto-Oncogene Proteins c-akt / metabolism
Receptors, Androgen / metabolism*
Signal Transduction*
TOR Serine-Threonine Kinases / metabolism*
Grant Support
ID/Acronym/Agency:
CA099115/CA/NCI NIH HHS; R03 CA099115/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/AR protein, human; 0/Androgens; 0/Fatty Acids, Omega-3; 0/Neoplasm Proteins; 0/Receptors, Androgen; 25167-62-8/Docosahexaenoic Acids; AAN7QOV9EA/Eicosapentaenoic Acid; EC 2.7.1.1/MTOR protein, human; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

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


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