Reference - Detail
| RRC ID | 44301 |
|---|---|
| Author | Arai MA, Fujimatsu T, Uchida K, Sadhu SK, Ahmed F, Ishibashi M. |
| Title | Hh signaling inhibitors from Vitex negundo; naturally occurring inhibitors of the GLI1-DNA complex. |
| Journal | Mol Biosyst |
| Abstract |
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. |
| Volume | 9(5) |
| Pages | 1012-8 |
| Published | 2013-5-1 |
| DOI | 10.1039/c3mb25567k |
| PMID | 23403897 |
| MeSH | Animals Blotting, Western Cell Line Cell Line, Tumor Cell Survival / drug effects DNA / metabolism Diterpenes / chemistry Diterpenes / pharmacology* Hedgehog Proteins / antagonists & inhibitors* Hedgehog Proteins / metabolism Humans Keratinocytes / cytology Keratinocytes / drug effects Keratinocytes / metabolism Mice Molecular Structure Patched Receptors Patched-1 Receptor Protein Binding / drug effects Proto-Oncogene Proteins c-bcl-2 / metabolism Receptors, Cell Surface / metabolism Signal Transduction / drug effects* Transcription Factors / metabolism Vitex / chemistry* Zinc Finger Protein GLI1 |
| IF | 3.336 |
| Times Cited | 20 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Resource | |
| Human and Animal Cells | 10T1/2(RCB0247) PANC-1(RCB2095) |