New hedgehog/GLI-signaling inhibitors from Adenium obesum

Midori A. Arai, Chikashi Tateno, Takashi Koyano, Thaworn Kowithayakorn, Seiichiro Kawabe, Masami Ishibashi

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The aberrant hedgehog (Hh)/GLI signaling pathway causes the formation and progression of a variety of tumors. We recently constructed a cell-based screening system to search for Hh/GLI signaling inhibitors from natural resources. Using our screening system, Adenium obesum was found to include Hh/GLI signaling inhibitors from our tropical plant extract libraries. Bioassay-guided fractionation of this plant extract led to the isolation of 17 cardiac glycosides (1-17), including 3 new compounds (4, 9, 16). These compounds showed strong inhibitory activities, especially the IC50 of 17 is 0.11 μM. The inhibition of GLI-related protein expression with 3, 9, 11, 15 and 17 was observed in human pancreatic cancer cells (PANC1), which express Hh/GLI components aberrantly. The expressions of GLI-related proteins PTCH and BCL2 were clearly inhibited. These compounds also showed selective cytotoxicity against two cancer cell lines, with less effect against normal cells (C3H10T1/2). RT-PCT examinations showed that Ptch mRNA expression by 3, 11, 15 and 17 was inhibited.

Original languageEnglish
Pages (from-to)1133-1139
Number of pages7
JournalOrganic and Biomolecular Chemistry
Volume9
Issue number4
DOIs
Publication statusPublished - 2011 Feb 21
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'New hedgehog/GLI-signaling inhibitors from Adenium obesum'. Together they form a unique fingerprint.

  • Cite this

    Arai, M. A., Tateno, C., Koyano, T., Kowithayakorn, T., Kawabe, S., & Ishibashi, M. (2011). New hedgehog/GLI-signaling inhibitors from Adenium obesum. Organic and Biomolecular Chemistry, 9(4), 1133-1139. https://doi.org/10.1039/c0ob00677g