Dehydroxymethylepoxyquinomicin selectively ablates T-CAEBV cells

Front Biosci (Landmark Ed). 2015 Jan 1;20(3):502-14. doi: 10.2741/4322.

Abstract

Chronic active Epstein-Barr virus infection (CAEBV) represents a new subtype of lymphoproliferative disorders characterized by high morbidity and mortality rates and often leads to malignant transformation of infected cells. Efficient therapeutic strategies are presently unavailable; therefore, the development of therapies to prevent CAEBV-mediated transformation and disease progression is crucial. Here, we used microarray analysis and luciferase reporter assays to reveal the potential role of activated nuclear factor kappa B (NF-kB) in T cell type of-CAEBV infection. Using a series of cellular and molecular experiments, we demonstrated that dehydroxymethylepoxyquinomicin (DHMEQ), a novel NF-kB inhibitor, can selectively induce apoptosis in SNT-16 cells infected with CAEBV. Mechanistic studies suggested that DHMEQ induces SNT-16 cell apoptosis through NF-kB inhibition coupled with oxidative stress generation. Thus, activated NF-kB could be a new target for CAEBV therapeutics. Owing to its selective targeting ability, DHMEQ may be a candidate for a novel therapeutic regimen to control the progression of CAEBV infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Base Sequence
  • Benzamides / pharmacology*
  • Cells, Cultured
  • Chronic Disease
  • Cyclohexanones / pharmacology*
  • DNA Primers
  • Epstein-Barr Virus Infections / genetics
  • Epstein-Barr Virus Infections / metabolism
  • Epstein-Barr Virus Infections / pathology*
  • Flow Cytometry
  • Gene Expression
  • Humans
  • NF-kappa B / metabolism
  • Oxidative Stress
  • Real-Time Polymerase Chain Reaction

Substances

  • Benzamides
  • Cyclohexanones
  • DNA Primers
  • NF-kappa B
  • dehydroxymethylepoxyquinomicin