Synthetic ω-3 epoxyfatty acids as antiproliferative and pro-apoptotic agents in human breast cancer cells

J Med Chem. 2014 Sep 11;57(17):7459-64. doi: 10.1021/jm501083y. Epub 2014 Aug 29.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Caspase 3 / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cyclin D1 / metabolism
  • Enzyme Activation / drug effects
  • Epoxy Compounds / chemical synthesis
  • Epoxy Compounds / chemistry
  • Epoxy Compounds / pharmacology
  • Fatty Acids, Omega-3 / chemical synthesis
  • Fatty Acids, Omega-3 / chemistry
  • Fatty Acids, Omega-3 / pharmacology*
  • Female
  • Humans
  • Immunoblotting
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Models, Chemical
  • Molecular Structure
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Epoxy Compounds
  • Fatty Acids, Omega-3
  • Cyclin D1
  • Adenosine Triphosphate
  • JNK Mitogen-Activated Protein Kinases
  • Caspase 3