Antitumorigenic Properties of Omega‑3 Endocannabinoid Epoxides Jahnabi Roy Josephine E. Watson In Sup Hong Timothy M. Fan Aditi Das 10.1021/acs.jmedchem.8b00243.s003 https://acs.figshare.com/articles/dataset/Antitumorigenic_Properties_of_Omega_3_Endocannabinoid_Epoxides/6683357 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. 2018-06-01 00:00:00 cannabinoid receptor 1 EDP-EA antimigratory CB 1-selective binding derivative regioisomer OS novel class Dietary omega -3 tumor FAAH antitumorigenic epoxide acid amide hydrolase DHA DHEA