The inhibition of NFκB is relevant to both apoptotic processes and inflammation, as discussed further below. NFκB and cell proliferation NFκB, a transcription factor represented by a series of subunits harbouring discrete DNA binding and transactivational

functionality, is implicated in both intrinsic and extrinsic apoptotic pathways (see [36] for review) and has been shown to prevent apoptosis as well as promote transformation in epithelial-derived cancers [37]. Mechanistically, in the absence of NFκB signalling, inhibitor-of-apoptosis proteins (IAPs) fail to suppress assembly of the death-inducing complex II, which allows for the TRADD-mediated activation of caspase-8 selleck screening library and subsequent apoptosis [36, 38]. Furthermore, IAPs can directly promote the ubiquitin-mediated degradation of the NFκB-inducing serine/threonine kinase (NIK), ultimately resulting in NFκB activation [39]. Although

a detailed discussion on this topic is out of scope, it is well established Kinase Inhibitor Library supplier that activated NFκB is associated with an anti-apoptotic pro-survival advantage which is relevant given our data showing that GTA+ve extracts reduced NFκB expression. These observations are consistent with the reported biological activity of the resolvins and protectins, which have been shown to exert both pro-apoptotic effects [40] and the resolution of inflammation by attenuating cytokine levels in an NFκB-dependent manner [41]. One limitation of our study was that we were unable to determine NFκB levels in RAW264.7 cells, which will require further investigation upon Sodium butyrate the generation of sufficient quantities

of either enriched extract, or more preferably, purified synthetic GTAs. However, the dramatic reduction of NFκB upon GTA treatment in colon tumor cells is highly relevant given the reduced levels of circulating GTAs in CRC patients [17, 18] and the well-established inflammatory component of this disease [42]. NFκB and inflammation Besides its anti-apoptotic role, NFκB represents a key link between inflammation and cancer (see [43] for review), and in particular, is considered a master regulator of intestinal immunological function and activator of factors involved in driving intestinal inflammation [44–46]. NFκB activation has been observed in numerous GI-related conditions including inflammatory bowel disease [47], Crohn’s disease [48], ulcerative colitis [35], inflamed intestinal mucosa [49] as well as CRC [50–53]. It has been shown that the NFκB transcriptional activity in gastric mucosa is induced during aging [53], that positive NFκB expression as assessed through immunohistochemistry is observed in 73.

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