The results shown here represent the first report of GTA biological activity, which revealed that cells treated with GTA+ve extracts had reduced proliferative capacity coinciding with PARP fragmentation, significantly down-regulated NFκB expression, increased IκBα levels, and numerous down-regulated inflammatory markers including nitric oxide, NOS2, IL-1β, TNFα and COX2. Given the critical role of NFκB in regulating both apoptosis and inflammation and its association with aging, our data

suggests that the protective effects of GTAs are mediated, at least in part, through NFκB signalling. A reduction of GTAs over time could therefore be involved in compromising one’s ability to protect against chronic Torin 1 cost inflammation and possibly cancer. GTAs, fatty acids, and proliferation Our observation that GTA+ve extracts dose-dependently reduce cell proliferation, accompanied by the appearance of multiple PARP cleavage products with different molecular weights in SW620 cells but only the 24 kDa fragment in MCF-7 cells, suggests a complex cell-specific interplay between different proteases. Although it has been reported that caspase-3 activation can result in the 89 and 24 kDa fragments and that cathepsin-b and granzyme-b can produce fragments of 50 and 64 kDa, respectively [23], further work will be required to investigate

Tozasertib concentration GTA-specific protease activation. Our evidence of apoptosis upon treatment with GTAs is consistent with numerous other reports showing pro-apoptotic effects mediated through polyunsaturated long chain fatty acids (PUFAs). STK38 For example, docosahexanaeoic acid (DHA) has been shown to promote apoptosis through numerous pathways including cytochrome-c mediated caspase activation [24, 25], inhibition of the regulatory subunit of PI3-kinase, and reduction of PTEN phosphorylation [24,

26]. Others have shown that DHA and the PUFA punicic acid ultimately exert their intrinsic effects through dissipation of the mitochondrial membrane potential [27, 28], and that DHA and butyrate can promote apoptosis by altering mitochondrial Ca2+ levels [29]. Treatment of various cell lines, for example LAPC-4 LB-100 purchase prostate cancer-derived cells, with PUFAs, has been shown to reduce proliferation and induce apoptosis [30]. There are also studies demonstrating the inhibitory effects of omega-3 PUFAs on growth and angiogenesis of chemically induced as well as transplanted tumor model systems [31–33]. The observation of reduced cell growth in the presence of GTA+ve extract is therefore consistent with a large body of literature showing similar effects with exposure to long-chain PUFAs (see [34] for review). In addition to its anti-proliferative effect, GTA+ve extract also protected against the LPS-mediated induction of several pro-inflammatory proteins including TNFα, IL-1β, NOS2 and COX2, and inhibited the production of nitric oxide.