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.
Umezawa
Kazuo
K
Faculty of Science and Technology, Keio University, Yokohama, Japan. umezawa@applc.keio.ac.jp
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects*; D003512:Cyclohexanones / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000378:metabolism*; D011809:Quinones / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001549:Benzamides; D003512:Cyclohexanones; D016328:NF-kappa B; D011809:Quinones; C464444:dehydroxymethylepoxyquinomicin; C111288:epoxyquinomicin C