Targeting NR4A1 (TR3) in cancer cells and tumors

Syng Ook Lee, Xi Li, Shaheen Khan, Stephen Safe

Research output: Contribution to journalReview article

56 Citations (Scopus)

Abstract

Introduction: Nuclear receptor 4A1(NR4A1) (testicular receptor 3 (TR3), nuclear hormone receptor (Nur)77) is a member of the nuclear receptor superfamily of transcription factors and is highly expressed in multiple tumor types. RNA interference studies indicate that NR4A1 exhibits growth-promoting, angiogenic and prosurvival activity in most cancers. Areas covered: Studies on several apoptosis-inducing agents that activate nuclear export of NR4A1, which subsequently forms a mitochondrial NR4A1-bcl-2 complex that induces the intrinsic pathway for apoptosis are discussed. Cytosporone B and related compounds that induce NR4A1-dependent apoptosis in cancer cells through both modulation of nuclear NR4A1 and nuclear export are discussed. A relatively new class of diindolylmethane analogs (C-DIMs) including 1,1-bis(3′-indolyl)- 1-(p-methoxyphenyl)methane (DIM-C-pPhOCH3) (NR4A1 activator) and 1,1-bis(3′-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH) (NR4A1 deactivator) are discussed in more detail. These anticancer drugs (C-DIMs) act strictly through nuclear NR4A1 and induce apoptosis in cancer cells and tumors. Expert opinion: It is clear that NR4A1 plays an important pro-oncogenic role in cancer cells and tumors, and there is increasing evidence that this receptor can be targeted by anticancer drugs that induce cell death via NR4A1-dependent and -independent pathways.Since many of these compounds exhibit relatively low toxicity, they represent an important class of mechanism-based anticancer drugs with excellent potential for clinical applications.

Original languageEnglish (US)
Pages (from-to)195-206
Number of pages12
JournalExpert Opinion on Therapeutic Targets
Volume15
Issue number2
DOIs
StatePublished - Feb 1 2011

Fingerprint

Cytoplasmic and Nuclear Receptors
Tumors
Cells
Neoplasms
Apoptosis
Cell Nucleus Active Transport
Pharmaceutical Preparations
Methane
Expert Testimony
Cell death
RNA Interference
Toxicity
Cell Death
Transcription Factors
Modulation
RNA

Keywords

  • anticancer activity
  • DIMs
  • NR4A1
  • Nur77
  • TR3

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

Cite this

Targeting NR4A1 (TR3) in cancer cells and tumors. / Lee, Syng Ook; Li, Xi; Khan, Shaheen; Safe, Stephen.

In: Expert Opinion on Therapeutic Targets, Vol. 15, No. 2, 01.02.2011, p. 195-206.

Research output: Contribution to journalReview article

Lee, Syng Ook ; Li, Xi ; Khan, Shaheen ; Safe, Stephen. / Targeting NR4A1 (TR3) in cancer cells and tumors. In: Expert Opinion on Therapeutic Targets. 2011 ; Vol. 15, No. 2. pp. 195-206.
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