title: Synthetic ω-3 epoxyfatty acids as antiproliferative and pro-apoptotic agents in human breast cancer cells.
abstract: ω-3-17,18-Epoxyeicosapentaenoic acid decreases cell proliferation and activates apoptosis, whereas its regioisomers stimulate growth. We evaluated synthetic ω-3 epoxides of saturated fatty acids as antiproliferative and pro-apoptotic agents in MDA-MB-231 breast cancer cells. The epoxides, but not their urea, amide, or carbamate isosteres, impaired ATP production, enhanced caspase-3 activity, and activated c-jun-N-terminal-kinase signaling, leading to cyclin D1 down-regulation and cell cycle arrest in G1-phase. Fatty acid ω-3 monoepoxides may represent a novel class of antitumor agents.
authors.affiliation: Discipline of Pharmacology, School of Medical Sciences, Sydney Medical School, University of Sydney , Sydney, New South Wales 2006, Australia.
authors.forename: Herryawan Ryadi Eziwar
authors.initials: HR
authors.lastname: Dyari
authors.forename: Tristan
authors.initials: T
authors.lastname: Rawling
authors.forename: Kirsi
authors.initials: K
authors.lastname: Bourget
authors.forename: Michael
authors.initials: M
authors.lastname: Murray
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008956:Models, Chemical; D015394:Molecular Structure; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004852:Epoxy Compounds; D015525:Fatty Acids, Omega-3; D019938:Cyclin D1; D000255:Adenosine Triphosphate; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3