ABSTRACT
NF-kB, nuclear factor kappa B; IkB, inhibitor of NF-kB; CAPE, caffeic acid phenethyl ester; PBIT; S,S0-l,4-Phenylene-bis (1,2ethanediyl) bis-isothiourea; PDTC, pyrrolidine dithocarbamate.
ABSTRACT
The process of tumorigenesis requires cellular transformation, hyperproliferation, invasion, angiogenesis, and metastasis. Several genes that mediate these processes are regulated by
the transcription factor NF-kB. The latter is activated by various carcinogens, inflammatory agents, and tumor promoters. The NF-kB, a transcription factor, is present normally in the cytoplasm as an inactive heterotrimer consisting of p50, p65, and IkBa subunits. When activated, NF-B migrates to the nucleus translocates to the as a p50-p65 heterodimer. This factor regulates the expression of various genes that control apoptosis, viral replication, tumorigenesis, various autoimmune diseases, and inflammation. The NF-kB has been linked to the development of carcinogenesis for several reasons. First, various carcinogens and tumor promoters have been shown to activate NF-kB. Second, activation of NF-kB has been shown to block apoptosis and promote proliferation. Third, the tumor microenvironment can induce NF-kB activation. Fourth, constitutive expression of NF-kB is frequently found in tumor cells. Fifth, NF-kB activation induces resistance to chemotherapeutic agents. Sixth, several genes involved in tumor initiation, promotion, and metastasis are regulated by NF-kB. Seventh, various chemopreventive agents have been found to downregulate the NF-kB activation. All these observations suggest that NF-kB could mediate tumorigenesis and thus can be used as a target for chemoprevention and for the treatment of cancer. Agents, which suppress NF-kB activation, can suppress the expression of genes involved in carcinogenesis and tumorigenesis in vivo.
