Orphan nuclear receptor Nur77 translocates to mitochondria in the early phase of apoptosis induced by synthetic chenodeoxycholic acid derivatives in human stomach cancer cell line SNU-1

Ann N Y Acad Sci. 2003 Dec;1010:171-7. doi: 10.1196/annals.1299.029.

Abstract

Apoptosis-inducing activity of synthetic CDCA derivatives, HS-1199 and HS-1200, on gastric cancer cell line SNU-1 cells was explored. CDCA derivatives demonstrated various apoptosis hallmarks, such as mitochondrial changes, activation of caspase, DNA fragmentation, and nuclear condensation. Importantly, the orphan receptor Nur77 (TR3) was shown to translocate from the nucleus to mitochondria at the early time points after CDCA derivatives treatment. These data support the theory that CDCA derivatives-induced apoptosis of SNU-1 gastric cancer cell lines is mediated by mitochondria and caspase, and, at least in part, by Nur77.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Chenodeoxycholic Acid / analogs & derivatives*
  • Chenodeoxycholic Acid / pharmacology*
  • DNA-Binding Proteins / metabolism*
  • Humans
  • In Situ Nick-End Labeling
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / physiology
  • Membrane Potentials / drug effects
  • Mitochondria / drug effects
  • Mitochondria / physiology*
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Protein Transport / drug effects
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Stomach Neoplasms
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • NR4A1 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Transcription Factors
  • Chenodeoxycholic Acid