Document Detail


Antiproliferative and antimigratory actions of synthetic long chain n-3 monounsaturated fatty acids in breast cancer cells that overexpress cyclooxygenase-2.
MedLine Citation:
PMID:  22822908     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cyclooxygenase-2 (COX-2) is overexpressed in many human cancers and converts the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid to prostaglandin E2 (PGE2), which drives tumorigenesis; in contrast, n-3 PUFA inhibit tumorigenesis. We tested the hypothesis that these anti-tumor actions of n-3 PUFA may involve the n-3 olefinic bond. n-3 Monounsaturated fatty acids (MUFAs) of chain length C16-C22 were synthesized and evaluated in MDA-MB-468 breast cancer cells that stably overexpressed COX-2 (MDA-COX-2 cells). Longer chain (C19-C22) n-3 MUFAs inhibited proliferation, activated apoptosis, decreased PGE2 formation and decreased cell invasion; C16-C18 analogues were less active. Molecular modeling showed that interactions of Arg120, Tyr355 and several hydrophobic amino acid residues in the COX-2 active site with C19-C22 MUFA analogues were favored. Thus, longer-chain n-3 MUFAs may be prototypes of novel anti-cancer agents that decrease the formation of PGE2 in tumor cells that contain high levels of COX-2.
Authors:
Pei H Cui; Tristan Rawling; Kirsi Bourget; Terry Kim; Colin C Duke; Munikumar R Doddareddy; David Hibbs; Fanfan Zhou; Bruce N Tattam; Nenad Petrovic; Michael Murray
Related Documents :
2626218 - Synaptosomal uptake of choline and of gamma-aminobutyric acid: effects of ethanol and o...
8312358 - Regulatory volume decrease of cultured human fibroblasts involves changes in intracellu...
9698528 - Effects of endotoxin challenge on hepatic amino acid transport during cancer.
7066178 - Reaction of cells cultured in vitro to different asbestos dusts of equal surface area b...
184988 - Gas chromatographic determination of urinary vanilglycolic acid, vanilglycol, vanilacet...
16658138 - The relative amounts and identification of some 2,4-dichlorophenoxyacetic acid metaboli...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-23
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  -     ISSN:  1520-4804     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

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


Previous Document:  T regulatory cells play a significant role in modulating MHC class I antibody-induced obliterative a...
Next Document:  Bismuth-catalyzed and doped silicon nanowires for one-pump-down fabrication of radial junction solar...