4-oxo docosahexaenoic acid

4-oxo Docosahexaenoic acid (4-oxo DHA) is a putative metabolite of DHA with antiproliferative and PPARγ agonist activity. It inhibits the growth of several triple-negative breast cancer cell lines [MCF-10F, trMCF, bsMCF, MDA-MB-231, and BT549] at 50-100 μM but increases the proliferation of MCF-7 cells. 4-oxo DHA binds covalently to PPARγ and activates gene transcription in luciferase reporter assays and dendritic cells with EC50 values of approximately 8-16 μM.

17-oxo-4(Z),7(Z),10(Z),13(Z),15(E),19(Z)-Docosahexaenoic acid is a metabolite of lipoxygenase-mediated oxidation of DHA that is produced endogenously by aspirin-enhanced COX-2 activity. It has been shown to activate Nrf2-dependent antioxidant gene expression, to act as a PPARγ agonist (EC50 = ~200 nM), and to inhibit pro-inflammatory cytokine and nitric oxide production at biological concentration ranges (5-25 μM).