Inhibition of tumor growth by NF-kappaB inhibitors

NF-kappaB is a transcription factor that induces inflammatory cytokines and anti-apoptotic proteins. NF-kappaB is often constitutively activated in human cancers and leukemias, which might increase the malignant character of neoplastic diseases. Therefore, NF-kappaB inhibitors might be useful as anticancer agents. Our research team designed a new NF-kappaB inhibitor that is based on the structure of the antibiotic epoxyquomicin C isolated from a microorganism. The designed compound, DHMEQ, inhibited the ligand-induced activation of NF-kappaB, and it also inhibited the constitutively activated NF-kappaB in cancer cells. DHMEQ is a unique inhibitor of NF-kappaB that acts at the level of the nuclear translocation. It inhibited both canonical and non-canonical NF-kappaB activating pathways. It inhibited various carcinomas and leukemias in animal models without any toxicity, and might be useful as an anticancer agent.