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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / biosynthesis
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Caspase 3 / metabolism
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Cell Cycle Checkpoints / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Cyclin D1 / metabolism
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Enzyme Activation / drug effects
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Epoxy Compounds / chemical synthesis
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Epoxy Compounds / chemistry
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Epoxy Compounds / pharmacology
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Fatty Acids, Omega-3 / chemical synthesis
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Fatty Acids, Omega-3 / chemistry
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Fatty Acids, Omega-3 / pharmacology*
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Female
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Humans
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Immunoblotting
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JNK Mitogen-Activated Protein Kinases / metabolism
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Models, Chemical
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Molecular Structure
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Signal Transduction / drug effects
Substances
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Antineoplastic Agents
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Epoxy Compounds
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Fatty Acids, Omega-3
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Cyclin D1
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Adenosine Triphosphate
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JNK Mitogen-Activated Protein Kinases
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Caspase 3