Abstract

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.

Original languageEnglish (US)
Pages (from-to)5569-5579
Number of pages11
JournalJournal of Medicinal Chemistry
Volume61
Issue number13
DOIs
StatePublished - Jul 12 2018

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Endocannabinoids
Epoxy Compounds
Cannabinoid Receptors
Docosahexaenoic Acids
Osteosarcoma
Omega-3 Fatty Acids
Neoplasms
Anti-Inflammatory Agents
Inflammation
Lung
Growth

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Antitumorigenic Properties of Omega-3 Endocannabinoid Epoxides. / Roy, Jahnabi; Watson, Josephine E.; Hong, In Sup; Fan, Timothy M; Das, Aditi.

In: Journal of Medicinal Chemistry, Vol. 61, No. 13, 12.07.2018, p. 5569-5579.

Research output: Contribution to journalArticle

Roy, Jahnabi ; Watson, Josephine E. ; Hong, In Sup ; Fan, Timothy M ; Das, Aditi. / Antitumorigenic Properties of Omega-3 Endocannabinoid Epoxides. In: Journal of Medicinal Chemistry. 2018 ; Vol. 61, No. 13. pp. 5569-5579.
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