*3.6. NF-kB Pathway*

NF-κB (Nuclear factor-κB) is involved in a variety of cellular mechanisms, such as death, growth, inflammation, and immune response. NF-κB mainly acts as a regulator of gene transcription in response to oxidative stress. The interaction with EGCG was described in a variety of cell models, both in vivo and in vitro [64]. NF-κB is one of the most investigated targets in cancer research and the interaction with this pathway should be considered to be a relevant topic in cancer treatment design. The inhibitory activity of EGCG on NF-κB has been demonstrated in a large number of independent studies. Studies that were performed in normal human epidermal keratinocytes in which EGCG was used at different concentration to modulate NF-κB activity, leading to a protective effect towards the negative cascade that was induced by UV radiation. This is considered the proof of the mechanism of action of green tea as a photoprotective agen<sup>t</sup> [92]. Moreover EGCG has been shown to reduce significantly the gu<sup>t</sup> mucosa inflammation in response to injury, thus inhibiting the production of inflammatory factors via the modulation of NF-κB expression and other involved genes [118]. The authors showed that, in ulcerative colitis (a refractory inflammatory disease of the large intestine) rat model, EGCG intraperitoneally administered at 50 mg/kg/d could reduce the severity of the disease, through the TLR4/MyD88/NF-κ<sup>B</sup> signaling pathway. Moving on cancer research, EGCG was able to activate caspases in epidermoid carcinoma cells, and this has been demonstrated to play a relevant role in the inhibition of NF-κB and induction of apoptosis [119]. Nevertheless, EGCG has been demonstrated to play a potential role in human colon cancer prevention inhibiting AP-1, c-fos, cyclin D1 promoters, and NF-κB activity in four different human colon cancer cell lines, with an IC50 value of about 20 μg/mL [74].
