Antitumor effect of a novel nuclear factor-kappa B activation inhibitor in bladder cancer cells.

Nuclear factor (NF)-κB is a transcription factor that not only induces and controls various genes, including those of inflammatory cytokines, but also activates genes which suppress apoptosis. It has been clearly demonstrated that certain advanced human bladder cancer cells constitutively acquire the ability to activate NF-κB, which not only protects cancer cells from apoptotic cell death, but also upregulates the production of various cytokines that may increase the malignant potential of the disease and cause paraneoplastic syndromes. The NF-κB inhibitors may therefore be useful as anticancer agents. An NF-κB function inhibitor, a dehydroxymethyl derivative of epoxyquinomicin C (DHMEQ), has recently been designed and synthesized. The effectiveness of DHMEQ against advanced human bladder cancer cell line KU-19-19, in which NF-κB is constitutively activated, has been investigated. The DNA-binding activity of NF-κB was completely inhibited following 2-6-h exposure to 10 μg/ml of DHMEQ. Marked levels of apo...