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Cyclooxygenase (COX) is an enzyme (EC 1.14.99.1) that is responsible for formation of important biological mediators called prostanoids (including prostaglandins, prostacyclin and thromboxane). Pharmacological inhibition of COX can provide relief from the

The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W, Dennison A. Eur J Cancer. 2009 Aug;45(12):2077-86. Epub 2009 Jun 1. Review. PMID: 19493674 Omega-3 fatty acid (omega-3 FA) consumption has long been associated with a lower incidence of colon, breast and prostate cancers in many human populations. Human trials have demonstrated omega-3 FA to have profound anti-inflammatory effects in those with cancer. In vitro and small animal studies have yielded a strong body of evidence establishing omega-3 FA as having anti-inflammatory, anti-apoptotic, anti-proliferative and anti-angiogenic effects. This review explores the evidence and the mechanisms by which omega-3 FA may act as angiogenesis inhibitors and identifies opportunities for original research trialling omega-3 FAs as anti-cancer agents in humans. The conclusions drawn from this review suggest that omega-3 FAs in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found principally in oily fish have potent anti-angiogenic effects inhibiting production of many important angiogenic mediators namely; Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF), Platelet-Derived Endothelial Cell Growth Factor (PDECGF), cyclo-oxygenase 2 (COX-2), prostaglandin-E2 (PGE2), nitric oxide, Nuclear Factor Kappa Beta (NFKB), matrix metalloproteinases and beta-catenin

Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer. Cerchietti LC, Navigante AH, Castro MA. Nutr Cancer. 2007;59(1):14-20. PMID: 17927497

The present study, thus, raises the possibility that DHA may exert pro-apoptotic and antitumoral effects through proteasomal regulation of beta-catenin levels and alterations in the expression of TCF-beta-catenin target genes. Docosahexaenoic acid induces proteasome-dependent degradation of beta-catenin, down-regulation of survivin and apoptosis in human colorectal cancer cells not expressing COX-2. Calviello G, Resci F, Serini S, Piccioni E, Toesca A, Boninsegna A, Monego G, Ranelletti FO, Palozza P. Carcinogenesis. 2007 Jun;28(6):1202-9. Epub 2006 Dec 20. PMID: 17183061 doi:10.1093/carcin/bgl254

Mice fed fish oil and curcumin showed a significantly reduced tumor volume, 25% (P < 0.04) and 43% (P < 0.005), respectively, and importantly, a combination of curcumin and fish oil diet showed > 72% (P < 0.0001) tumor volume reduction. Expression and activity of iNOS, COX-2, and 5-LOX are downregulated, and p21 is upregulated in tumor xenograft fed curcumin combined with fish oil diet when compared to individual diets. The preceding results evidence for the first time that curcumin combined with omega-3 fatty acids provide synergistic pancreatic tumor inhibitory properties. Prevention and treatment of pancreatic cancer by curcumin in combination with omega-3 fatty acids. Swamy MV, Citineni B, Patlolla JM, Mohammed A, Zhang Y, Rao CV. Nutr Cancer. 2008;60 Suppl 1:81-9. PMID: 19003584

In biochemistry, eicosanoids are signaling molecules derived from omega-3 (ω-3) or omega-6 (ω-6) fats. They exert complex control over many bodily systems, especially in inflammation, immunity and as messengers in the central nervous system. The network

Effects of dietary flaxseed on intestinal tumorigenesis in Apc(Min) mouse. Bommareddy A, Zhang X, Schrader D, Kaushik RS, Zeman D, Matthees DP, Dwivedi C. Nutr Cancer. 2009;61(2):276-83. PMID: 19235044 DOI: 10.1080/01635580802419764

Prostacyclin (or PGI2) is a member of the family of lipid molecules known as eicosanoids.\nAs a drug, it is also known as "epoprostenol".[1] The terms are sometimes used interchangeably Prostacyclin (PGI2) chiefly prevents formation of the platelet plug involved in primary hemostasis (a part of blood clot formation). It is also an effective vasodilator. Prostacyclin's interactions in contrast to thromboxane (TXA2), another eicosanoid, strongly suggest a mechanism of cardiovascular homeostasis between the two hormones in relation to vascular damage.

Prostate tumor growth and recurrence can be modulated by the omega-6:omega-3 ratio in diet: athymic mouse xenograft model simulating radical prostatectomy. Kelavkar UP, Hutzley J, Dhir R, Kim P, Allen KG, McHugh K. Neoplasia. 2006 Feb;8(2):112-24. PMID: 16611404

Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. Arita M, Bianchini F, Aliberti J, Sher A, Chiang N, Hong S, Yang R, Petasis NA, Serhan CN. J Exp Med. 2005 Mar 7;201(5):713-22. PMID: 15753205 oi:10.1084/jem.20042031

A plethora of research documents the role of chronic inflammatory mediators such as 5-lipooxygenase (5-LOX) and tumor necrosis factor-alpha (TNF-α) in the manifestation and progression of prostate and other cancers.7-19,30,31,33,49,52-54,87,88 The typical American diet is high in omega-6 fatty acids, saturated fats, and arachidonic acid. Over-consumption of these foods, and under-consumption of omega-3 fatty acids, contribute significantly to systemic chronic inflammatory states. Boswellia extracts have been thoroughly studied as natural remedies for inflammatory disorders. A patented extract from boswellia called 5-LOXIN® has potent ability to inhibit the enzyme 5-LOX, preventing the formation of protein-degrading enzymes, and protecting against inflammation-induced events that can promote tumor angiogenesis.

Krieger NS, Parker WR, Alexander KM, Bushinsky DA. Prostaglandins regulate acid-induced cell-mediated bone resorption. Am J Physiol Renal Physiol. 2000 Dec;279(6):F1077-82. Erratum in: Am J Physiol Renal Physiol 2001 Sep;281(3):section F following tabl

Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells. Habbel P, Weylandt KH, Lichopoj K, Nowak J, Purschke M, Wang JD, He CW, Baumgart DC, Kang JX. World J Gastroenterol. 2009 Mar 7;15(9):1079-84. PMID: 19266600 doi: 10.3748/wjg.15.1079.

Egg consumption in relation to cardiovascular disease and mortality: the Physicians' Health Study. Djoussé L, Gaziano JM. Am J Clin Nutr. 2008 Apr;87(4):964-9. PMID: 18400720 Results: In an average follow-up of 20 y, 1550 new myocardial infarctions (MIs), 1342 incident strokes, and 5169 deaths occurred. Egg consumption was not associated with incident MI or stroke in a multivariate Cox regression. In contrast, adjusted hazard ratios (95% CI) for mortality were 1.0 (reference), 0.94 (0.87, 1.02), 1.03 (0.95, 1.11), 1.05 (0.93, 1.19), and 1.23 (1.11, 1.36) for the consumption of < 0.0001). This association was stronger among diabetic subjects, in whom the risk of death in a comparison of the highest with the lowest category of egg consumption was twofold (hazard ratio: 2.01; 95% CI: 1.26, 3.20; P for interaction = 0.09). Conclusions: Infrequent egg consumption does not seem to influence the risk of CVD in male physicians. In addition, egg consumption was positively related to mortality, more strongly so in diabetic subjects, in the study population.

Targeting lipoxygenases with care. de Souza PM, Newson J, Gilroy DW. Chem Biol. 2006 Nov;13(11):1121-2. PMID: 17113992 doi:10.1016/j.chembiol.2006.11.002  

Controlling the resolution of acute inflammation: a new genus of dual anti-inflammatory and proresolving mediators. Serhan CN. J Periodontol. 2008 Aug;79(8 Suppl):1520-6. Review. PMID: 18673006 doi:10.1902/jop.2008.080231

Fatty acid facts, part III: Cardiovascular disease, or, a fish diet is noy fishy. Pauwels EK, Kostkiewicz M. Drug News Perspect. 2008 Dec;21(10):552-61. PMID: 19221636

Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations and Alzheimer's disease. Bazan NG. Lipid Res. 2008 Nov 18. [Epub ahead of print] PMID: 19018037

March 7, 2005 Boston, MA - The anti-inflammatory effect of fish oils appears to be due to a powerful anti-inflammatory compound called resolvin (resolution-phase interaction product) E1, which is produced from eicosapentaenoic acid (EPA), Dr Makoto Arita (Brigham and Women's Hospital and Harvard Medical School, Boston, MA) and colleagues report in the March 7, 2005 issue of the Journal of Experimental Medicine [1]. Arita writes, "At nanomolar levels, resolvin E1 dramatically reduced dermal inflammation, peritonitis, dendritic cell migration, and interleukin (IL)-12 production.

Fish oil-derived fatty acids, docosahexaenoic acid and docosapentaenoic acid, and the risk of acute coronary events: the Kuopio ischaemic heart disease risk factor study. Rissanen T, Voutilainen S, Nyyssönen K, Lakka TA, Salonen JT. Circulation. 2000 Nov 28;102(22):2677-9. PMID: 11094031 Methods and Results-We studied this association in the Kuopio Ischaemic Heart Disease Risk Factor Study, a prospective population study in Eastern Finland. Subjects were randomly selected and included 1871 men aged 42 to 60 years who had no clinical coronary heart disease at baseline examination. A total of 194 men had a fatal or nonfatal acute coronary event during follow-up. In a Cox proportional hazards' model adjusting for other risk factors, men in the highest fifth of the proportion of serum DHA+DPA in all fatty acids had a 44% reduced risk (P=0.014) of acute coronary events compared with men in the lowest fifth. Men in the highest fifth of DHA+DPA who had a low hair content of mercury (2.0 µg/g). There was no association between proportion of eicosapentaenoic acid and the risk of acute coronary events. Conclusions-Our data provide further confirmation for the concept that fish oil-derived fatty acids reduce the risk of acute coronary events. However, a high mercury content in fish could attenuate this protective effect.