The synthetic epoxyquinoids jesterone dimer and epoxyquinone A monomer induce apoptosis and inhibit REL (human c-Rel) DNA binding in an IκBα-deficient diffuse large B-cell lymphoma cell line

Mei-Chih Liang, Sujata Bardhan, John A. Porco, Thomas D. Gilmore*

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The NF-κB transcription factor signaling pathway is constitutively active in many human cancers, and inhibition of this pathway can often kill cancer cells by inducing apoptosis. In this study, we show that two synthetic epoxyquinoids, jesterone dimer (JD) and epoxyquinone A monomer (EqM), are equally effective at inhibiting the growth of two human lymphoma cell lines that have constitutively nuclear REL (human c-Rel) DNA-binding complexes, but either express (SUDHL-4 cells) or do not express (RC-K8 cells) the NF-κB inhibitor IκBα. Furthermore, in these cells, both JD and EqM dose-dependently induced apoptosis, inhibited REL DNA-binding activity, and converted REL to a high molecular weight form. In A293 cells, JD and EqM inhibited the DNA-binding activity of overexpressed REL, but not p50. Replacement of Cys-27 with Ser in REL reduced JD- and EqM-mediated inhibition of REL DNA-binding activity. These results suggest that JD and EqM can induce apoptosis in IκBα-deficient lymphoma cells through a mechanism involving direct inhibition of transcription factor REL.

Original languageEnglish
Pages (from-to)69-78
Number of pages10
JournalCancer Letters
Volume241
Issue number1
DOIs
StatePublished - 8 Sep 2006

Keywords

  • Epoxyquinoid
  • Epoxyquinone A monomer
  • Jesterone dimer
  • Lymphoma
  • NF-kappaB
  • REL

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