Anticancer effects of n-3 EPA and DHA and their endocannabinoid derivatives on breast cancer cell growth and invasion

Iain Brown, Jisun Lee, Alan A. Sneddon, Maria G. Cascio, Roger G. Pertwee, Klaus W.J. Wahle, Dino Rotondo, Steven D. Heys

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The anticancer effects of the omega-3 long chain polyunsaturated fatty acids (LCPUFA), EPA and DHA may be due, at least in part, to conversion to their respective endocannabinoid derivatives, eicosapentaenoyl-ethanolamine (EPEA) and docosahexaenoyl-ethanolamine (DHEA). Here, the effects of EPEA and DHEA and their parent compounds, EPA and DHA, on breast cancer (BC) cell function was examined. EPEA and DHEA exhibited greater anti-cancer effects than EPA and DHA in two BC cells (MCF-7 and MDA-MB-231) whilst displaying no effect in non-malignant breast cells (MCF-10a). Both BC lines expressed CB 1/2 receptors that were responsible, at least partly, for the observed anti-proliferative effects of the omega-3 endocannabinoids as determined by receptor antagonism studies. Additionally, major signalling mechanisms elicited by these CB ligands included altered phosphorylation of p38-MAPK, JNK, and ERK proteins. Both LCPUFAs and their endocannabinoids attenuated the expression of signal proteins in BC cells, albeit to different extents depending on cell type and lipid effectors. These signal proteins are implicated in apoptosis and attenuation of BC cell migration and invasiveness. Furthermore, only DHA reduced in vitro MDA-MB-231 migration whereas both LCPUFAs and their endocannabinoids significantly inhibited invasiveness. This finding was consistent with reduced integrin β3 expression observed with all treatments and reduced MMP-1 and VEGF with DHA treatment. Attenuation of cell viability, migration and invasion of malignant cells indicates a potential adjunct nutritional therapeutic use of these LCPUFAs and/or their endocannabinoids in treatment of breast cancer.

Original languageEnglish
Article number102024
Pages (from-to)102024
Number of pages10
JournalProstaglandins, Leukotrienes and Essential Fatty Acids
Early online date16 Oct 2019
Publication statusPublished - May 2020

Bibliographical note


We would like to acknowledge NHS Grampian Endowment funds and TENOVUS Scotland for funding. JL was funded by a scholarship from Fraserburgh Moonlight Prowl and AAS was funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS). We also thank Dr Raphael Mechoulam, University of Jerusalem, for the gift of the endocannabinoids.


  • Omega (N)-3 Fatty Acids
  • N-acylethanolamides (NAEs)
  • Endocannabinoids
  • Breast Cancer
  • Cannabinoid Receptors (CBRs)
  • MAP kinase signalling
  • cell proliferation
  • Cell proliferation
  • Omega (N)-3 fatty acids
  • Cannabinoid receptors (CBRs)
  • Breast cancer
  • P38 MAPK


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