Hh signaling inhibitors from Vitex negundo; Naturally occurring inhibitors of the GLI1-DNA complex

Midori A. Arai, Teruhisa Fujimatsu, Kyoko Uchida, Samir K. Sadhu, Firoj Ahmed, Masami Ishibashi

研究成果: Article査読

28 被引用数 (Scopus)

抄録

The hedgehog (Hh) signaling pathway has crucial roles in embryonic development, cell maintenance and proliferation, and is also known to contribute to cancer cell growth. New naturally occurring Hh inhibitors (1, 7 and 9) were isolated from Vitex negundo using our previously constructed cell-based assay. Bioactivity guided isolation provided 9 natural compounds including a new diterpene, nishindanol (9). Compounds 7 and 9 showed cytotoxicity against cancer cell lines in which Hh signaling was aberrantly activated. Vitetrifolin D (7; GLI1 transcriptional inhibition IC50 = 20.2 μM) showed inhibition of Hh related protein (PTCH and BCL2) production. Interestingly, the constructed electrophoresis mobility shift assay revealed that vitetrifolin D (7) disrupted GLI1 binding on its DNA binding domain. epi-Sclareol (8; inactive), possessing a similar structure to 7, did not show inhibition of GLI1-DNA complex formation. This is the first example of naturally occurring inhibitors of GLI1-DNA complex formation.

本文言語English
ページ(範囲)1012-1018
ページ数7
ジャーナルMolecular BioSystems
9
5
DOI
出版ステータスPublished - 2013 5月
外部発表はい

ASJC Scopus subject areas

  • バイオテクノロジー
  • 分子生物学

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