t-AUCB, an improved sEH inhibitor, suppresses human glioblastoma cell growth by activating NF-κB-p65

J Neurooncol. 2012 Jul;108(3):385-93. doi: 10.1007/s11060-012-0841-4. Epub 2012 Mar 2.


Although sEH inhibitors are well studied in inflammatory and cardiovascular diseases, their effects on gliomas are unclear. In this study, we investigated the effects of t-AUCB, a more potent and selective sEH inhibitor, on U251 and U87 human glioblastoma cell lines and the HepG2 human hepatocellular carcinoma cell line. Our results showed that t-AUCB efficiently inhibited sEH activities in all three cell lines (the inhibition rate was more than 80% in each) and suppressed U251 and U87 cell growth in a dose-dependent manner, but exhibited no cell growth inhibition on HepG2. We detected high levels of phosphorylated NF-κB-p65 (Ser536) in t-AUCB-treated U251 and U87 cells, and then found that the NF-κB inhibitor PDTC can completely abolish t-AUCB-induced growth inhibition. This indicated that t-AUCB suppresses U251 and U87 cell growth by activating NF-κB-p65. Moreover, we found that t-AUCB induces cell-cycle G0/G1 phase arrest by regulating Cyclin D1 mRNA and protein levels and CDC2 (Thr161) phosphorylation level. We propose to further test this promising reagent for its anti-glioma activity in clinical relevant orthotopic brain glioma models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Benzoates / pharmacology*
  • Blotting, Western
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Epoxide Hydrolases / antagonists & inhibitors*
  • Flow Cytometry
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Phosphorylation / drug effects
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Urea / analogs & derivatives*
  • Urea / pharmacology


  • 4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid
  • Benzoates
  • CCND1 protein, human
  • NF-kappa B
  • RNA, Messenger
  • Cyclin D1
  • Urea
  • Epoxide Hydrolases