Inhibition of tumor growth by NF-kappaB inhibitors

Cancer Sci. 2006 Oct;97(10):990-5. doi: 10.1111/j.1349-7006.2006.00285.x. Epub 2006 Aug 22.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Benzamides / chemistry
  • Cell Proliferation / drug effects*
  • Cyclohexanones / chemistry
  • Drug Design*
  • Humans
  • NF-kappa B / antagonists & inhibitors*
  • Neoplasms / metabolism*
  • Quinones / chemistry
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Benzamides
  • Cyclohexanones
  • NF-kappa B
  • Quinones
  • dehydroxymethylepoxyquinomicin
  • epoxyquinomicin C