Induction and intracellular localization of Nur77 dictate fenretinide-induced apoptosis of human liver cancer cells

Hui Yang, Nathan Bushue, Pengli Bu, Yu-Jui Yvonne Wan

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Fenretinide, a synthetic retinoid, is known to induce apoptosis in various cancer cells. However, the mechanism by which fenretinide induces apoptosis remains unclear. The current study examines the mechanisms of fenretinide-induced apoptosis in human hepatoma cells. The induction of Nur77 and the cytoplasmic distribution of Nur77 induced by fenretinide were positively correlated with the apoptotic effect of fenretinide in HCC cells. The sensitivity of Huh-7 cells was related to Nur77 translocation and targeting mitochondria, whereas the mechanism of resistance for HepG2 cells seemed due to Nur77 accumulating in the nucleus. The intracellular location of Nur77 was also associated with the differential capability of fenretinide-induced ROS generation in these two cell lines. In addition, the knockdown of Nur77 expression by siRNA greatly reduced fenretinide-induced apoptosis and cleaved caspase 3 in Huh- 7 cells. Therefore, our findings demonstrate that fenretinide-induced apoptosis of HCC cells is Nur77 dependent and that the intracellular localization of Nur77 dictates the sensitivity of the HCC cells to fenretinide-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)948-954
Number of pages7
JournalBiochemical Pharmacology
Volume79
Issue number7
DOIs
StatePublished - Apr 1 2010
Externally publishedYes

Keywords

  • Apoptosis
  • Fenretinide
  • Nuclear receptor
  • Nur77
  • Retinoids
  • ROS

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

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