Broussochalcone a is a novel inhibitor of the orphan nuclear receptor nr4a1 and induces apoptosis in pancreatic cancer cells

Hyo Seon Lee, Soo Hyun Kim, Bo Mi Kim, Stephen Safe, Syng Ook Lee

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The orphan nuclear receptor 4A1 (NR4A1) is overexpressed in pancreatic cancer and exhibits pro-oncogenic activity, and NR4A1 silencing and treatment with its inactivators has been shown to inhibit pancreatic cancer cells and tumor growth. In this study, we identified broussochal-cone A (BCA) as a new NR4A1 inhibitor and demonstrated that BCA inhibits cell growth partly by inducing NR4A1-mediated apoptotic pathways in human pancreatic cancer cells. BCA downreg-ulated specificity protein 1 (Sp1)-mediated expression of an anti-apoptotic protein, survivin, and activated the endoplasmic reticulum (ER) stress-mediated apoptotic pathway. These results suggest that NR4A1 inactivation contributes to the anticancer effects of BCA, and that BCA represents a potential anticancer agent targeting NR4A1 that is overexpressed in many types of human cancers.

Original languageEnglish (US)
Article number2316
JournalMolecules
Volume26
Issue number8
DOIs
StatePublished - Apr 2 2021

Keywords

  • Apoptosis
  • Broussochalcone A
  • ER stress
  • NR4A1
  • Pancreatic cancer
  • Sp1

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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