895127-66-9Relevant academic research and scientific papers
Antitumorigenic Properties of Omega-3 Endocannabinoid Epoxides
Roy, Jahnabi,Watson, Josephine E.,Hong, In Sup,Fan, Timothy M.,Das, Aditi
, p. 5569 - 5579 (2018/06/11)
Accumulating studies have linked inflammation to tumor progression. Dietary omega-3 fatty acids, such as docosahexaenoic acid (DHA), have been shown to suppress tumor growth through their conversion to epoxide metabolites. Alternatively, DHA is converted enzymatically into docosahexaenoylethanolamide (DHEA), an endocannabinoid with antiproliferative activity. Recently, we reported a novel class of anti-inflammatory DHEA-epoxide derivative called epoxydocospentaenoic-ethanolamide (EDP-EA) that contain both ethanolamide and epoxide moieties. Herein, we study the antitumorigenic properties of EDP-EAs in an osteosarcoma (OS) model. First, we show ～80% increase in EDP-EAs in metastatic versus normal lungs of mice. We found significant differences in the apoptotic and antimigratory potencies of the different EDP-EA regioisomers, which were partially mediated through cannabinoid receptor 1 (CB1). Next, we synthesized derivatives of the most pro-apoptotic regioisomer. These derivatives had reduced hydrolytic susceptibility to fatty acid amide hydrolase (FAAH) and increased CB1-selective binding. Collectively, we report a novel class of EDP-EAs that exhibit antiangiogenic, antitumorigenic, and antimigratory properties in OS.
Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450
Lucas, Daniele,Goulitquer, Sophie,Marienhagen, Jan,Fer, Maude,Dreano, Yvonne,Schwaneberg, Ulrich,Amet, Yolande,Corcos, Laurent
experimental part, p. 1125 - 1133 (2010/09/16)
Cytochromes P450 (CYPs) metabolize polyun-saturated long-chain fatty acids (PUFA-LC) to several classes of oxygenated metabolites. Through use of human recombinant CYPs, we recently showed that CYP1A1, -2C19, -2D6, -2E1, and -3A4 are mainly hydroxylases, whereas CYP1A2, -2C8, -2C9, and -2J2 are mainly epoxygenases of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), respectively. It is worth noting that the last double bond of these PUFAs, i.e., ω6 in AA or ω3 in EPA and DHA, respectively, was preferentially epoxidized. In this study, we have characterized the stereoselectivity of this epoxidation reaction by comparison with the PUFA-LC epoxide stereoisomers obtained from the enantioselective bacterial CYP102A1 F87V. The stereoselectivity of the epoxidation of the last olefi n of AA (ω6), EPA (ω3), or DHA (ω3) differed between the CYP isoforms but was similar for EPA and DHA. These data give additional insight into the PUFA-LC epoxide enantiomers generated by the hepatic CYPs. Copyright
