New Hedgehog/GLI signaling inhibitors from Excoecaria agallocha

Yusnita Rifai, Midori A. Arai, Samir K. Sadhu, Firoj Ahmed, Masami Ishibashi

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The inhibition of the Hedgehog (Hh) signaling pathway has emerged as an anti-cancer strategy. Three flavonoid glycosides including 2 new compounds (1-2) were isolated from Excoecaria agallocha as Hedgehog/GLI1-mediated transcriptional inhibitors and exhibited cytotoxicity against human pancreatic (PANC1) and prostate (DU145) cancer cells. Our data revealed that compound 1 clearly inhibited the expression of GLI-related proteins (PTCH and BCL-2) and blocked the translocation of GLI1 transcription factors into the nucleus in PANC1. Deleting the Smoothened (Smo) function in PANC1 treated with 1 led to downregulation of the mRNA expression of Ptch. This study describes the first Hh signaling inhibitor which blocks GLI1 movement into the nucleus without interfering with Smo.

Original languageEnglish
Pages (from-to)718-722
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number2
DOIs
Publication statusPublished - 2011 Jan 15
Externally publishedYes

Keywords

  • Excoecaria agallocha
  • GLI1-mediated transcriptional activity
  • Hedgehog
  • Inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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