55833-27-7Relevant academic research and scientific papers
Antiproliferative and antimigratory actions of synthetic long chain n-3 monounsaturated fatty acids in breast cancer cells that overexpress cyclooxygenase-2
Cui, Pei H.,Kirsi Bourget, Tristan Rawing,Kim, Terry,Duke, Colin C.,Doddareddy, Munikumar R.,Hibbs, David E.,Zhou, Fanfan,Tattam, Bruce N.,Petrovic, Nenad,Murray, Michael
, p. 7163 - 7172 (2012/11/07)
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 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 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 anticancer agents that decrease the formation of PGE2 in tumor cells that contain high levels of COX-2.
