A small molecule inhibitor of NF-kappaB, dehydroxymethylepoxyquinomicin (DHMEQ), suppresses growth and invasion of nasopharyngeal carcinoma (NPC) cells

Cancer Lett. 2010 Jan 1;287(1):23-32. doi: 10.1016/j.canlet.2009.05.022. Epub 2009 Jun 26.

Abstract

Despite the demonstrated constitutive activation of NF-kappaB in nasopharyngeal carcinoma (NPC), the therapeutic potential of targeting this pathway has not been investigated. Here, we employed a small molecule inhibitor of NF-kappaB, DHMEQ (which mainly blocks nuclear translocation of activated NF-kappaB) and demonstrated significant inhibition of NPC cell proliferation, migration, invasion, as well as anchorage-independent growth. These antitumor effects were associated with induction of G(2)/M cell cycle arrest and apoptosis, and downregulation of NF-kappaB target genes (EGFR, cyclin D1 and survivin). This first demonstration of therapeutic benefits of NF-kappaB targeting in NPC implicates the importance of targeting this pathway in NPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Benzamides / pharmacology*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cyclohexanones / pharmacology*
  • G2 Phase / drug effects
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Matrix Metalloproteinase 9 / genetics
  • NF-kappa B / antagonists & inhibitors*
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / pathology
  • Neoplasm Invasiveness
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Benzamides
  • Cyclohexanones
  • NF-kappa B
  • Vascular Endothelial Growth Factor A
  • dehydroxymethylepoxyquinomicin
  • Intercellular Adhesion Molecule-1
  • Matrix Metalloproteinase 9