Role of linoleic acid-derived oxylipins in cancer
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Role of linoleic acid-derived oxylipins in cancer Matthew L. Edin 1 & Caroline Duval 1 & Guodong Zhang 2 & Darryl C. Zeldin 1
# This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2020
“While LA consumption has been promoted by some to protect against cardiovascular disease, recent data suggests that cytochrome P450-mediated metabolism of LA to pro-inflammatory and pro-angiogenic oxylipins may have deleterious effects on tumor growth and metastasis.” In recent decades, dietary guidance has advocated reducing the intake of total and saturated fats, elimination of trans fats, and replacement with polyunsaturated fats. Increasing intake of the essential fatty acid linoleic acid (LA) lowers low-density lipoprotein cholesterol and also lowers the risk of hypertension [1]. Thus, LA is considered a “cardiovascular-friendly” essential dietary fatty acid, and American consumption of LA containing vegetable oils has increased significantly over the past century [2]. However, dietary LA intake is controversial, as increasing LA consumption fails to protect against cardiovascular diseases or reduce all-cause mortality [2]. In addition, the effects of increased LA consumption on other diseases are less well studied. While LA consumption has been promoted by some to protect against cardiovascular disease, recent data suggests that cytochrome P450-mediated metabolism of LA to proinflammatory and pro-angiogenic oxylipins may have deleterious effects on tumor growth and metastasis. Cytochromes P450 of the CYP2C and CYP2J subfamilies can oxidize polyunsaturated fatty acids to form bioactive epoxy fatty acid (EpFAs). The most widely studied EpFAs are the arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), which have potent cardioprotective effects. The effects of EETs are diminished by microsomal and soluble epoxide hydrolases (mEH and sEH, respectively), which hydrolyze EET to less-active diols (dihydroxyeicosatrienoic acids, DHETs) [3, 4]. The vasodilatory, anti-inflammatory, anti* Darryl C. Zeldin [email protected] 1
Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, Building 101, Room A214, Research Triangle Park, Durham, NC 27709, USA
2
Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA
apoptotic, and cardioprotective effects of EETs suggest that sEH inhibitors (sEHi) may be beneficial for the treatment of cardiovascular diseases; however, EET-induced cellular proliferation, migration, and angiogenesis may promote tumor growth and metastasis [5]. In humans, dietary LA is the precursor of AA formation. CYP2C and CYP2J enzymes can also metabolize LA to EpFAs termed epoxyoctadecamonoenoic acids (EpOMES) which are hydrolyzed to corresponding diols dihyroxyoctadecamonoenoic acids (DiHOMEs). EpOMEs and DiHOMEs are produced by many cell types and are far more abundant in tissues and plasma than EETs and DHETs. EpOMEs and DiHOMEs are
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