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

Cui, PH; Kirsi Bourget, TR; Kim, T; Duke, CC; Doddareddy, MR; Hibbs, DE; Zhou, F; Tattam, BN; Petrovic, N; Murray, M

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

Cui, PH Kirsi Bourget, TR

Kim, T Duke, CC Doddareddy, MR Hibbs, DE Zhou, F Tattam, BN Petrovic, N Murray, M

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Publication Type:: Journal Article
Citation:: Journal of Medicinal Chemistry, 2012, 55 (16), pp. 7163 - 7172
Issue Date:: 2012-08-23

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Field	Value	Language
dc.contributor.author	Cui, PH	en_US
dc.contributor.author	Kirsi Bourget, TR https://orcid.org/0000-0002-6624-6586	en_US
dc.contributor.author	Kim, T	en_US
dc.contributor.author	Duke, CC	en_US
dc.contributor.author	Doddareddy, MR	en_US
dc.contributor.author	Hibbs, DE	en_US
dc.contributor.author	Zhou, F	en_US
dc.contributor.author	Tattam, BN	en_US
dc.contributor.author	Petrovic, N	en_US
dc.contributor.author	Murray, M	en_US
dc.date.issued	2012-08-23	en_US
dc.identifier.citation	Journal of Medicinal Chemistry, 2012, 55 (16), pp. 7163 - 7172	en_US
dc.identifier.issn	0022-2623	en_US
dc.identifier.uri	http://hdl.handle.net/10453/28484
dc.description.abstract	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. © 2012 American Chemical Society.	en_US
dc.relation.ispartof	Journal of Medicinal Chemistry	en_US
dc.relation.isbasedon	10.1021/jm300673z	en_US
dc.subject.classification	Medicinal & Biomolecular Chemistry	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Breast Neoplasms	en_US
dc.subject.mesh	Neoplasm Invasiveness	en_US
dc.subject.mesh	Collagen	en_US
dc.subject.mesh	Proteoglycans	en_US
dc.subject.mesh	Fatty Acids, Omega-3	en_US
dc.subject.mesh	Dinoprostone	en_US
dc.subject.mesh	Laminin	en_US
dc.subject.mesh	Antineoplastic Agents	en_US
dc.subject.mesh	Drug Combinations	en_US
dc.subject.mesh	Drug Screening Assays, Antitumor	en_US
dc.subject.mesh	Apoptosis	en_US
dc.subject.mesh	Cell Proliferation	en_US
dc.subject.mesh	Cell Movement	en_US
dc.subject.mesh	Catalytic Domain	en_US
dc.subject.mesh	Structure-Activity Relationship	en_US
dc.subject.mesh	Thermodynamics	en_US
dc.subject.mesh	Models, Molecular	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Cyclooxygenase 2	en_US
dc.subject.mesh	Hydrophobic and Hydrophilic Interactions	en_US
dc.title	Antiproliferative and antimigratory actions of synthetic long chain n-3 monounsaturated fatty acids in breast cancer cells that overexpress cyclooxygenase-2	en_US
dc.type	Journal Article
utslib.citation.volume	16	en_US
utslib.citation.volume	55	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
utslib.for	0304 Medicinal and Biomolecular Chemistry	en_US
utslib.for	0305 Organic Chemistry	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	closed_access
pubs.issue	16	en_US
pubs.publication-status	Published	en_US
pubs.volume	55	en_US

Abstract:

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. © 2012 American Chemical Society.

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http://hdl.handle.net/10453/28484