Possible role of peritoneal NF-κB in peripheral inflammation and cancer: lessons from the inhibitor DHMEQ.

NF-κB is a transcription factor and considered to be involved in the mechanisms of inflammation and cancer. We have designed the new NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ), which directly binds to a specific cysteine residue of Rel family proteins to inhibit their DNA-binding activity. DHMEQ showed potent anti-inflammatory and anticancer activities in many animal models. So far DHMEQ has been administered mainly into the peritoneal cavity of animals. According to the limited distribution of DHMEQ in the peritoneal cavity after intraperitoneal administration, it is likely that NF-κB in the peritoneal cells would be the main target of DHMEQ. Therefore, the inflammatory cells in the peritoneal cavity appear important for the regulation of peripheral inflammation and tumor growth in the body, and peritoneal NF-κB may be an important target for anti-inflammatory and anticancer agents in future.