論文 - 詳細
| RRC ID | 37549 |
|---|---|
| 著者 | Arai MA, Uchida K, Sadhu SK, Ahmed F, Koyano T, Kowithayakorn T, Ishibashi M. |
| タイトル | Hedgehog inhibitors from Artocarpus communis and Hyptis suaveolens. |
| ジャーナル | Bioorg Med Chem |
| Abstract |
The hedgehog (Hh) signaling pathway plays crucial roles in cell maintenance and proliferation during embryonic development. Naturally occurring Hh inhibitors were isolated from Artocarpus communis and Hyptis suaveolens using our previously constructed cell-based assay system. Bioactivity guided fractionation led to the isolation of 15 compounds, including seven new compounds (4, 5, 6, 7, and 9-11). The isolated compounds showed cytotoxicity against a cancer cell line (PANC1) in which Hh signaling was abnormally activated. Several compounds (12-14; GLI1 transcriptional inhibition IC50=7.6, 4.7, and 4.0 μM, respectively) inhibited Hh related protein (BCL2) expression. Moreover, compounds 1, 12, and 13 disrupted GLI1 and DNA complex formation. |
| 巻・号 | 23(15) |
| ページ | 4150-4154 |
| 公開日 | 2015-8-1 |
| DOI | 10.1016/j.bmc.2015.06.058 |
| PII | S0968-0896(15)00552-0 |
| PMID | 26178912 |
| MeSH | Antineoplastic Agents, Phytogenic / chemistry* Antineoplastic Agents, Phytogenic / pharmacology* Artocarpus / chemistry* Biological Products / chemistry Biological Products / pharmacology Cell Line, Tumor DNA / metabolism Drug Screening Assays, Antitumor / methods Electrophoretic Mobility Shift Assay Hedgehog Proteins / antagonists & inhibitors* Hedgehog Proteins / metabolism Humans Hyptis / chemistry* Inhibitory Concentration 50 Magnetic Resonance Spectroscopy Molecular Structure Signal Transduction / drug effects Transcription Factors / metabolism Zinc Finger Protein GLI1 |
| IF | 3.073 |
| 引用数 | 9 |
| WOS 分野 | CHEMISTRY, MEDICINAL CHEMISTRY, ORGANIC BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | 10T1/2(RCB0247) |