2. Academic Validation
  3. Antiproliferative and antimigratory actions of synthetic long chain n-3 monounsaturated fatty acids in breast cancer cells that overexpress cyclooxygenase-2

Antiproliferative and antimigratory actions of synthetic long chain n-3 monounsaturated fatty acids in breast cancer cells that overexpress cyclooxygenase-2

  • J Med Chem. 2012 Aug 23;55(16):7163-72. doi: 10.1021/jm300673z.
Pei H Cui 1,  Tristan Rawling,  Kirsi Bourget,  Terry Kim,  Colin C Duke,  Munikumar R Doddareddy,  David E Hibbs,  Fanfan Zhou,  Bruce N Tattam,  Nenad Petrovic,  Michael Murray
Affiliations

Affiliation

  • 1 Pharmacogenomics and Drug Development Group, Faculty of Pharmacy, University of Sydney, NSW 2006, Australia.
PMID: 22822908 DOI: 10.1021/jm300673z
Abstract

Cyclooxygenase-2 (COX-2) is overexpressed in many human cancers and converts the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid to prostaglandin E(2) (PGE(2)), which drives tumorigenesis; in contrast, n-3 PUFA inhibit tumorigenesis. We tested the hypothesis that these antitumor 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 PGE(2) 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 Anticancer agents that decrease the formation of PGE(2) in tumor cells that contain high levels of COX-2.

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