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"Ann Arbor, MI - New laboratory research suggests that the COX-2 inhibitor celecoxib (Celebrex, Pfizer), might impede the action of "baby" aspirin [1]. Dr Gilad Rimon (University of Michigan, Ann Arbor) and colleagues found evidence that this was the case in a dog model and say that "it will be important to determine" whether the same is true in humans. The report was published online December 1, 2009 in the Proceedings of the National Academy of Medicine. Celecoxib is the only COX-2 inhibitor to have remained on the market in the US, and doctors who recommend this painkiller often coprescribe a daily low dose of 81 mg of aspirin (known as a "baby" dose) to counteract any possible prothrombotic effects of the coxib, while minimizing potential gastrointestinal toxicity of the aspirin. Senior author of the new work, Dr William L Smith (University of Michigan, Ann Arbor), explained to heartwire that previous studies in humans have shown that celecoxib does not interfere with the effect of a standard dose of aspirin (325 mg), but any potential interaction of celecoxib with the lower dose has not been examined. Stagger dosing to avoid any potential problems First, Smith explained that he and his colleagues looked in vitro at celecoxib and found that it binds to one of two available sites on the COX-1 enzyme. "This surprised us," he commented. "It appears to interfere with the ability of some other drugs to affect COX-1, most notably aspirin." Second, in beagles, they administered the dog-equivalent of a baby dose of aspirin in humans and then gave some of the animals the equivalent of 100 mg of celecoxib twice daily in addition. "Celecoxib plus aspirin interfered with the normal effect of low-dose aspirin on platelets," he notes. Smith says this observation obviously requires confirmation in humans, but in the meantime he suggests "getting around the problem" by patients taking the low-dose aspirin at least 15 to 30 minutes before the celecoxib is taken, "because

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

"ScienceDaily (Jan. 13, 2010) - For those who do not drink, researchers have found that six essential oils -from thyme, clove, rose, eucalyptus, fennel and bergamot -- can suppress the inflammatory COX-2 enzyme, in a manner similar to resveratrol, the chemical linked with the health benefits of red wine. They also identified that the chemical carvacrol was primarily responsible for this suppressive activity."

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

Thromboxane B2 is an inactive metabolite/product of thromboxane A2. It is almost completely cleared in the urine. It itself is not involved in platelet activation and aggregation in case of a wound, but its precursor, thromboxane A2, is. Thromboxane A2 synthesis is the target of the drug aspirin, which inhibits the COX-1 enzyme (the source of thromboxane A2 in platelets).

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

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

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.

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

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

Li N, Sood S, Wang S, Fang M, Wang P, Sun Z, Yang CS, Chen X. Overexpression of 5-lipoxygenase and cyclooxygenase 2 in hamster and human oral cancer and chemopreventive effects of zileuton and celecoxib. Clin Cancer Res. 2005 Mar 1;11(5):2089-96. PMID

Sun Z, Sood S, Li N, Ramji D, Yang P, Newman RA, Yang CS, Chen X. Involvement of the 5-lipoxygenase/leukotriene A4 hydrolase pathway in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch, and inhibition of carcinoge

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

Bushinsky DA, Parker WR, Alexander KM, Krieger NS. Metabolic, but not respiratory, acidosis increases bone PGE(2) levels and calcium release. Am J Physiol Renal Physiol. 2001 Dec;281(6):F1058-66. PMID: 11704556 [PubMed - indexed for MEDLINE]