Chemopreventive Agents Induce Suppression of Nuclear Factor‐κB Leading to Chemosensitization

Publisher Website
Google Scholar
Abstract
Nuclear factor-κB (NF-κB), a transcription factor, is present normally in the cytoplasm as an inactive heterotrimer consisting of p50, p65, and IκBα subunits. When activated, NF-κB translocates to the nucleus as a p50-p65 heterodimer. This factor regulates the expression of various genes that control apoptosis, viral replication, tumorigenesis, various autoimmune diseases, and inflammation. NF-κB has been linked to the development of carcinogenesis for several reasons. First, various carcinogens and tumor promoters have been shown to activate NF-κB. Second, activation of NF-κB has been shown to block apoptosis and promote proliferation. Third, the tumor microenvironment can induce NF-κB activation. Fourth, constitutive expression of NF-κB is frequently found in tumor cells. Fifth, NF-κB activation induces resistance to chemotherapeutic agents. Sixth, several genes involved in tumor initiation, promotion, and metastasis are regulated by NF-κB. Seventh, various chemopreventive agents have been found to down-regulate the NF-κB activation. All these observation suggest that NF-κB could mediate tumorigenesis and thus can be used as a target for chemoprevention and for the treatment of cancer. Agents that suppress NF-κB activation can suppress the expression of genes involved in carcinogenesis and tumorigenesis in vivo.