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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(9):1584-91C

Abstract

The omega-3 fatty acid ethanolamides, docosahexaenoyl ethanolamide (DHEA) and eicosapentaenoyl ethanolamide (EPEA), displayed greater anti-proliferative potency than their parent omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in LNCaP and PC3 prostate cancer cells. DHEA and EPEA activated cannabinoid CB(1) and CB(2) receptors in vitro with significant potency, suggesting that they are endocannabinoids. Both LNCaP and PC3 cells expressed CB(1) and CB(2) receptors, and the CB(1)- and CB(2)-selective antagonists, AM281 and AM630, administered separately or together, reduced the anti-proliferative potencies of EPEA and EPA but not of DHEA or DHA in PC3 cells and of EPA but not of EPEA, DHEA or DHA in LNCaP cells. Even so, EPEA and EPA may not have inhibited PC3 or LNCaP cell proliferation via cannabinoid receptors since the anti-proliferative potency of EPEA was well below the potency it displayed as a CB(1) or CB(2) receptor agonist. Indeed, these receptors may mediate a protective effect because the anti-proliferative potency of DHEA in LNCaP and PC3 cells was increased by separate or combined administration of AM281 and AM630. The anandamide-metabolizing enzyme, fatty acid amide hydrolase (FAAH), was highly expressed in LNCaP but not PC3 cells. Evidence was obtained that FAAH metabolizes EPEA and DHEA and that the anti-proliferative potencies of these ethanolamides in LNCaP cells can be enhanced by inhibiting this enzyme. Our findings suggest that the expression of cannabinoid receptors and of FAAH in some tumour cells could well influence the effectiveness of DHA and EPA or their ethanolamide derivatives as anticancer agents.

Authors+Show Affiliations

Cancer Medicine Research Programme, Translational Medical Sciences, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Polwarth Building, Aberdeen, AB25 2ZD, UK. i.brown@abdn.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20660502

Citation

Brown, Iain, et al. "Cannabinoid Receptor-dependent and -independent Anti-proliferative Effects of Omega-3 Ethanolamides in Androgen Receptor-positive and -negative Prostate Cancer Cell Lines." Carcinogenesis, vol. 31, no. 9, 2010, pp. 1584-91.
Brown I, Cascio MG, Wahle KW, et al. 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(9):1584-91.
Brown, I., Cascio, M. G., Wahle, K. W., Smoum, R., Mechoulam, R., Ross, R. A., ... Heys, S. D. (2010). Cannabinoid receptor-dependent and -independent anti-proliferative effects of omega-3 ethanolamides in androgen receptor-positive and -negative prostate cancer cell lines. Carcinogenesis, 31(9), pp. 1584-91. doi:10.1093/carcin/bgq151.
Brown I, et al. 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(9):1584-91. PubMed PMID: 20660502.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid receptor-dependent and -independent anti-proliferative effects of omega-3 ethanolamides in androgen receptor-positive and -negative prostate cancer cell lines. AU - Brown,Iain, AU - Cascio,Maria G, AU - Wahle,Klaus W J, AU - Smoum,Reem, AU - Mechoulam,Raphael, AU - Ross,Ruth A, AU - Pertwee,Roger G, AU - Heys,Steven D, Y1 - 2010/07/25/ PY - 2010/7/28/entrez PY - 2010/7/28/pubmed PY - 2010/10/1/medline SP - 1584 EP - 91 JF - Carcinogenesis JO - Carcinogenesis VL - 31 IS - 9 N2 - The omega-3 fatty acid ethanolamides, docosahexaenoyl ethanolamide (DHEA) and eicosapentaenoyl ethanolamide (EPEA), displayed greater anti-proliferative potency than their parent omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in LNCaP and PC3 prostate cancer cells. DHEA and EPEA activated cannabinoid CB(1) and CB(2) receptors in vitro with significant potency, suggesting that they are endocannabinoids. Both LNCaP and PC3 cells expressed CB(1) and CB(2) receptors, and the CB(1)- and CB(2)-selective antagonists, AM281 and AM630, administered separately or together, reduced the anti-proliferative potencies of EPEA and EPA but not of DHEA or DHA in PC3 cells and of EPA but not of EPEA, DHEA or DHA in LNCaP cells. Even so, EPEA and EPA may not have inhibited PC3 or LNCaP cell proliferation via cannabinoid receptors since the anti-proliferative potency of EPEA was well below the potency it displayed as a CB(1) or CB(2) receptor agonist. Indeed, these receptors may mediate a protective effect because the anti-proliferative potency of DHEA in LNCaP and PC3 cells was increased by separate or combined administration of AM281 and AM630. The anandamide-metabolizing enzyme, fatty acid amide hydrolase (FAAH), was highly expressed in LNCaP but not PC3 cells. Evidence was obtained that FAAH metabolizes EPEA and DHEA and that the anti-proliferative potencies of these ethanolamides in LNCaP cells can be enhanced by inhibiting this enzyme. Our findings suggest that the expression of cannabinoid receptors and of FAAH in some tumour cells could well influence the effectiveness of DHA and EPA or their ethanolamide derivatives as anticancer agents. SN - 1460-2180 UR - https://www.unboundmedicine.com/medline/citation/20660502/Cannabinoid_receptor_dependent_and__independent_anti_proliferative_effects_of_omega_3_ethanolamides_in_androgen_receptor_positive_and__negative_prostate_cancer_cell_lines_ L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/bgq151 DB - PRIME DP - Unbound Medicine ER -