Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer

Nuclear factor-κB and inhibitor of κB kinase pathways in oncogenic initiation and progression

“…A number of other reports using a variety of chemotherapies and a variety of approaches to blocking NF-kB support this model (Baldwin, 2001;Yamamoto and Gaynor, 2001;Karin et al, 2002;Nakanishi and Toi, 2005). The recent review by Nakanishi and Toi (2005) provides a thorough outline of different chemotherapies that activate NF-kB and of compounds that can be used to block NF-kB activation to promote cancer therapy efficacy.…”

“…These include compounds that have already been approved for use in therapy, compounds that are undergoing clinical trials and compounds that show therapeutic promise in preliminary studies (see below). In summary, extensive evidence demonstrates that compounds which block NF-kB activation can serve to block cancer cell growth (Baldwin, 2001;Yamamoto and Gaynor, 2001;Karin et al, 2002;Gilmore and Herscovitch, 2006).…”

“…Another NF-kB inhibitor, the natural product parthenolide, has also shown efficacy against human AML stem and progenitor cells (Guzman et al, 2005), and cholangiocarcinoma cells (Kim et al, 2005b). Finally, a number of well-established dietary chemopreventive compounds have been shown to inhibit NF-kB (Yamamoto and Gaynor, 2001). It should be noted that a caution with some of these studies is that the therapeutic effects of certain inhibitors may involve the regulation of non-NF-kB targets.…”

“…Evidence was presented in the mid-1990s that DNAdamaging and stress-inducing agents activate NF-kB (see Baldwin, 2001;Yamamoto and Gaynor, 2001;Karin et al, 2002;Nakanishi and Toi, 2005). For example, NF-kB activation is seen in response to the chemotherapeutic compound daunorubicin and to irradiation (Wang et al, 1996).…”

Effects of dietary protein levels on the disease resistance, immune function and physical barrier function in the gill of grass carp ( Ctenopharyngodon idella ) after challenged with Flavobacterium columnare

“…Correlation analysis indicated that the mRNA levels of pro-inflammatory cytokines TNF-a, IL-1b, IL-8, IFN-g2 and IL-12p40 were positively correlated with the mRNA levels of NF-kB P65 and NF-kB P52 in the gills of grass carp ( Table 5). The nuclear translocation of NF-kB may be inhibited by IkBa in humans [69], and Heissmeyer et al [70] reported that the IKK complex (including IKKa, IKKb and IKKg) catalyses IkBa degradation in 293 cells. In the present study, compared with low or high levels of protein, we found that the optimal levels of dietary protein led to the down-regulation of IKKa, IKKb and IKKg mRNA levels and the up-regulation of IkBa mRNA level in the gills of grass carp.…”