Inducible cyclooxygenase inhibition

Hong CH, Sun KH, Jin O, Sun SK, Kyung AN, Sang KL. Evaluation of natural products on inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) in cultured mouse macrophage cells. J Ethnopharmacol 2002 83 153-159. 

Hwang D, Fischer NH, Jang BC, Tak H, Kim JK, Lee W. (1996). Inhibition of the expression of inducible cyclooxygenase and proinflammatory cytokines by sesquiterpene lactones in macrophages correlates with the inhibition of MAP kinases. Biochem Biophys Res Common. 226(3) 810-18. 

Hsueh CT, Chiu CF, Kelsen DP, et al. Selective inhibition of cyclooxygenase-2 enhances mitomycin-C-induced apoptosis. Cancer Chemother Pharmacol 2000 45 389-396. 

Classically, inflammation is a protective reaction of the body in response to some physical, chemical, or microbial injury and insult of the cells. Acute inflammation, rapid onset and shorter duration, is considered as a healthy response. However, when inflammation continues for prolonged period of time, it becomes detrimental and may raise the first step of a chronic disease (Medzhitov, 2008). Arachidonic acid/COX and nuclear factor- (NF- ) are well known inflammatory pathways which induce production of inflammatory mediators such as prostaglandins, thromboxanes, leukotrienes, and cytokines. Most commonly accepted mechanism of anti-inflammation is inhibition of cyclooxygenase (COX) activity. There are two kinds of cyclooxygenases COX-1 is natural protective enzyme of intestinal mucosa while COX-2 is induced by tissue damage as an inflammatory mediator (Maroon et al., 2006). NF- is a recently identified... 

Sulindac shows no relevant inhibition of cyclooxygenase (Warner et al., 1999), whereas the active metabolite sulindac sulfide shows inhibition of both isoenzymes with a preference for COX-1 in a whole blood assay (see also Brideau et al., 1996 ratio COX-1/COX-2 = 0.1). Sulindac is one of the NSAIDs, extensively studied in cancer reseach (Haanen, 2001). The metabolite sulindac sulfone induces apoptosis in tumor cells. 

Hata, Y., Pancho, L.R., Nojima, H. and Kimura, I. (1998) Endothelium dependent potentiation of prostaglandin F2a-induced contractions by ( )-[6]-gingeroI is inhibited by cyclooxygenase but not lipoxygenase inhibitors in mouse mesenteric veins. Biological and Pharmaceutical Bulletin 21 (8), 792-794. 

A major signalling pathway involves activation of a protein kinase that phosphorylates inhibitor kB proteins (IkBs) that normally inhibit the function of the nuclear transcription factor NFkB. Phosphorylation of IkB by the serine/threonine-specific IkB kinases (IKKs) leads to NFkB de-inhibition, nuclear translocation and expression of pro-inflammatory proteins such as inducible cyclooxygenase (iCOX) (which generates prostaglandins), inducible nitric oxide synthase (iNOS) (which generates vasodilatory and toxic free radicalgenerating NO) and pro-inflammatory cytokines. 

Metz, N., Lobstein, A., Schneider, Y., Gosse, R, Schleiffer, R., Anton, R., and Paul, R, Suppression of azoxymethane-induced preneoplastic lesions and inhibition of cyclooxygenase 2 activity in the colonic mucosa of rats drinking a crude green tea extract, Nutr. Cancer, 38 (1), 60-64, 2000. 

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