Terpenoids and a flavonoid glycoside from Acacia pennata leaves as hedgehog/GLI-mediated transcriptional inhibitors

Yusnita Rifai, Midori A. Arai, Takashi Koyano, Thaworn Kowithayakorn, Masami Ishibashi

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Overexpression of glioma-associated oncogene 1 (GLI1), which has been characterized as a terminal effector and a target gene of the Hedgehog (Hh) signaling pathway, is associated with the development of cancer. A cellular screen was applied utilizing of a GLI-dependent luciferase reporter in human keratinocyte cells (HaCaT) and identified two terpenoids (1 and 2) and a flavonoid glycoside (5) from Acacia pennata as Hh/GLI inhibitors. Compounds 1, 2, and 5 exhibited selective cytotoxicity against human pancreatic (PANC1) and prostate (DU145) cancer cells with no toxic effect on normal cells. This result was consistent with a dose-dependent reduction of the protein levels of antiapoptotic BCL-2 and the tumor suppressor patched 1 protein (PTCH). Additionally, treatment of 1 downregulated mRNA expression of Ptch in PANC1, suggesting that the compound has an inhibitory effect on the transcription of Hh/GLI.

Original languageEnglish
Pages (from-to)995-997
Number of pages3
JournalJournal of Natural Products
Volume73
Issue number5
DOIs
Publication statusPublished - 2010 May 28
Externally publishedYes

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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