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

doi:10.1016/j.plefa.2019.102024

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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Abstract

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 language	English
Article number	102024
Pages (from-to)	102024
Number of pages	10
Journal	Prostaglandins, Leukotrienes and Essential Fatty Acids
Volume	156
Early online date	16 Oct 2019
DOIs	https://doi.org/10.1016/j.plefa.2019.102024
Publication status	Published - May 2020

Bibliographical note

Acknowledgements

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.

Keywords

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
ACTIVATION
HUMAN PROSTATE
CANNABIDIOL
INDUCED APOPTOSIS
ANANDAMIDE
P38 MAPK
DEATH
CANNABINOID RECEPTOR
ETHANOLAMIDES
MODULATION

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

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Brown_et_al_PLEFA_Anticancer_effects_AAM
© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Accepted author manuscript, 709 KBLicence: CC BY-NC-ND

Cite this

@article{95185b85d3cb43c4aff62ae2f2961a9a,

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

abstract = "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. ",

keywords = "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, ACTIVATION, HUMAN PROSTATE, CANNABIDIOL, INDUCED APOPTOSIS, ANANDAMIDE, P38 MAPK, DEATH, CANNABINOID RECEPTOR, ETHANOLAMIDES, MODULATION",

author = "Iain Brown and Jisun Lee and Sneddon, {Alan A.} and Cascio, {Maria G.} and Pertwee, {Roger G.} and Wahle, {Klaus W.J.} and Dino Rotondo and Heys, {Steven D.}",

note = "Acknowledgements 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{\textquoteright}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.",

year = "2020",

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doi = "10.1016/j.plefa.2019.102024",

language = "English",

volume = "156",

pages = "102024",

journal = "Prostaglandins, Leukotrienes and Essential Fatty Acids",

issn = "0952-3278",

publisher = "Churchill Livingstone",

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TY - JOUR

T1 - Anticancer effects of n-3 EPA and DHA and their endocannabinoid derivatives on breast cancer cell growth and invasion

AU - Brown, Iain

AU - Lee, Jisun

AU - Sneddon, Alan A.

AU - Cascio, Maria G.

AU - Pertwee, Roger G.

AU - Wahle, Klaus W.J.

AU - Rotondo, Dino

AU - Heys, Steven D.

N1 - Acknowledgements 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.

PY - 2020/5

Y1 - 2020/5

N2 - 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.

AB - 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.

KW - Omega (N)-3 Fatty Acids

KW - N-acylethanolamides (NAEs)

KW - Endocannabinoids

KW - Breast Cancer

KW - Cannabinoid Receptors (CBRs)

KW - MAP kinase signalling

KW - cell proliferation

KW - Cell proliferation

KW - Omega (N)-3 fatty acids

KW - Cannabinoid receptors (CBRs)

KW - Breast cancer

KW - ACTIVATION

KW - HUMAN PROSTATE

KW - CANNABIDIOL

KW - INDUCED APOPTOSIS

KW - ANANDAMIDE

KW - P38 MAPK

KW - DEATH

KW - CANNABINOID RECEPTOR

KW - ETHANOLAMIDES

KW - MODULATION

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U2 - 10.1016/j.plefa.2019.102024

DO - 10.1016/j.plefa.2019.102024

M3 - Article

C2 - 31679810

SN - 0952-3278

VL - 156

SP - 102024

JO - Prostaglandins, Leukotrienes and Essential Fatty Acids

JF - Prostaglandins, Leukotrienes and Essential Fatty Acids

M1 - 102024

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

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Alan Sneddon

Iain Fraser Cytometry Centre

Cite this

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Profiles

Alan Sneddon

Equipment

Iain Fraser Cytometry Centre

Cite this