Omega-3 (n-3) fatty acids inhibit breast and prostate cancer cell growth. We previously showed that N-acylethanolamine derivatives of n-3 (n-3-NAE) are endocannabinoids, which regulate cancer cell proliferation. These n-3-NAE are synthesised in certain cells/tissues, after supplementing with fatty acids, however, no one has assessed whether and to what extent this occurs in cancer cells. We determined levels of endogenous n-3-NAEs in hormone sensitive and insensitive prostate and breast cancer cells and subsequent effects on other endocannabinoids (anandamide and 2-arachidonoylglycerol), before and after supplementing with DHA and EPA fatty acids, using HPLC tandem mass spectrometry. This is the first study reporting that n-3-NAEs are synthesised from their parent n-3 fatty acids in cancer cells, regardless of tumour type, hormone status or the presence of fatty acid amide hydrolase. This could have important implications for the use of n-3 fatty acids as therapeutic agents in breast and prostate cancers expressing cannabinoid receptors.
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- The CB1 cannabinoid receptor is coupled to the activation of protein kinase B/Akt.Biochem. J. 2000; 347: 369-373
- Cannabinoid receptor agonist-induced apoptosis of human prostate cancer cells LNCaP proceeds through sustained activation of ERK1/2 leading to G1 cell cycle arrest.J. Biol. Chem. 2006; 281: 39480-39491
- The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation.Proc. Natl. Acad. Sci. U.S.A. 1998; 95: 8375-8380
- Anti-proliferative and apoptotic effects of anandamide in human prostatic cancer cell lines: implication of epidermal growth factor receptor down-regulation and ceramide production.Prostate. 2003; 56: 1-12
- Cannabinoid receptor as a novel target for the treatment of prostate cancer.Cancer Res. 2005; 65: 1635-1641
- Overexpression of cannabinoid receptors CB1 and CB2 correlates with improved prognosis of patients with hepatocellular carcinoma.Cancer Genet. Cytogenet. 2006; 171: 31-38
- Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer.Mol. Cancer. Ther. 2009; 8: 3117-3129
- Isolation and structure of a brain constituent that binds to the cannabinoid receptor.Science. 1992; 258: 1946-1949
- Effect of polyunsaturated fatty acids on the growth of murine colon adenocarcinomas in vitro and in vivo.Br. J. Cancer. 1994; 70: 6-10
- Docosahexaenoic acid (DHA), a primary tumor suppressive omega-3 fatty acid, inhibits growth of colorectal cancer independent of p53 mutational status.Nutr. Cancer. 2007; 58: 178-187
- Effect of eicosapentaenoic acid on the proliferation and incidence of apoptosis in the colorectal cell line HT29.Lipids. 1999; 34: 1287-1295
- Exogenous supplementation with omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA; 22:6n-3) synergistically enhances taxane cytotoxicity and downregulates Her-2/neu (c-erbB-2) oncogene expression in human breast cancer cells.Eur. J. Cancer Prev. 2005; 14: 263-270
- Docosahexaenoic acid enhances the efficacy of docetaxel in prostate cancer cells by modulation of apoptosis: the role of genes associated with the NF-kappaB pathway.Prostate. 2008; 68: 1635-1646
- Influence of dietary fatty acids on endocannabinoid and N-acylethanolamine levels in rat brain, liver and small intestine.Biochim. Biophys. Acta. 1781; 2008: 200-212
- Anandamide and diet: inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets.Proc. Natl. Acad. Sci. U.S.A. 2001; 98: 6402-6406
- Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma.J. Lipid Res. 2010; 51: 1416-1423
- Anandamide and other N-acylethanolamines in human tumors.Lipids. 2002; 37: 907-912
- Docosahexaenoic acid and eicosapentaenoic acid are converted by 3T3-L1 adipocytes to N-acyl ethanolamines with anti-inflammatory properties.Biochim. Biophys. Acta. 1801; 2010: 1107-1114
- Cannabinoid receptor-dependent and -independent anti-proliferative effects of omega-3 ethanolamides in androgen receptor-positive and -negative prostate cancer cell lines.Carcinogenesis. 2010; 31: 1584-1591
- Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides.J. Biol. Chem. 2002; 277: 44877-44885
- Plasma anandamide and other N-acylethanolamines are correlated with their corresponding free fatty acid levels under both fasting and non-fasting conditions in women.Nutr. Metab. (London). 2010; 7: 49
- Effect of omega-3 fatty acid supplementation on the arachidonic acid:eicosapentaenoic acid ratio.Pharmacotherapy. 2007; 27: 633-638
- Enhancing cytotoxic therapies for breast and prostate cancers with polyunsaturated fatty acids.Nutr. Cancer. 2010; 62: 284-296
Published online: October 13, 2011
Accepted: September 20, 2011
Received in revised form: September 19, 2011
Received: March 4, 2011
☆Sources of support: This work was supported by Grants from the National Institutes of Health (DA-009789), TENOVUS Scotland, and NHS Grampian Endowments fund.
© 2011 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.