論文 - 詳細
| RRC ID | 71977 |
|---|---|
| 著者 | Arai MA, Tateno C, Koyano T, Kowithayakorn T, Kawabe S, Ishibashi M. |
| タイトル | New hedgehog/GLI-signaling inhibitors from Adenium obesum. |
| ジャーナル | Org Biomol Chem |
| 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 IC(50) 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. |
| 巻・号 | 9(4) |
| ページ | 1133-9 |
| 公開日 | 2011-2-21 |
| DOI | 10.1039/c0ob00677g |
| PMID | 21170436 |
| MeSH | Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology Apocynaceae / chemistry* Cell Line, Tumor Cell Survival / drug effects Hedgehog Proteins / antagonists & inhibitors* Humans Molecular Structure Oncogene Proteins / antagonists & inhibitors* Oncogene Proteins / genetics Signal Transduction / drug effects* Structure-Activity Relationship Trans-Activators / antagonists & inhibitors* Trans-Activators / genetics Zinc Finger Protein GLI1 |
| IF | 3.412 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 10T1/2(RCB0247) PANC-1(RCB2095) |