論文 - 詳細
| RRC ID | 43481 |
|---|---|
| 著者 | Arai MA, Tateno C, Hosoya T, Koyano T, Kowithayakorn T, Ishibashi M. |
| タイトル | Hedgehog/GLI-mediated transcriptional inhibitors from Zizyphus cambodiana. |
| ジャーナル | Bioorg Med Chem |
| Abstract |
The aberrant hedgehog (Hh)/GLI signaling pathway causes the formation and progression of a variety of tumors. By screening tropical plant extracts by using our screening system, Zizyphus cambodiana was found to include Hh/GLI signaling inhibitors. Bioassay-guided fractionation of this plant extract led to the isolation of three active pentacyclic triterpenes, colubrinic acid (1), betulinic acid (2) and alphitolic acid (3), as potent inhibitors. The inhibition of GLI-related protein expression with 1 or 2 was observed in HaCaT cells with exogenous GLI1, or human pancreatic cancer cells (PANC1), which express Hh/GLI components aberrantly. The expressions of GLI-related proteins PTCH and BCL2 were clearly inhibited by 1 or 2. We also examined the cytotoxicity of these active compounds against PANC1, human prostate cancer cells (DU145) and mouse embryo fibroblast cells (C3H10T1/2). The cytotoxicity against cancer cells (PANC1 and DU145) by 1 or 2 would be caused by inhibition of the expression of the anti-apoptosis protein BCL2. These pentacyclic triterpene inhibitors showed an important relationship between Hh/GLI signaling inhibition, the decrease of BCL2, and cytotoxicity against cancer cells. |
| 巻・号 | 16(21) |
| ページ | 9420-4 |
| 公開日 | 2008-11-1 |
| DOI | 10.1016/j.bmc.2008.09.053 |
| PII | S0968-0896(08)00904-8 |
| PMID | 18842418 |
| MeSH | Animals Betulinic Acid Blotting, Western Cell Survival / drug effects Cells, Cultured Fibroblasts / drug effects Humans Male Maytansine / analogs & derivatives Maytansine / chemistry Maytansine / pharmacology Mice Oncogene Proteins / antagonists & inhibitors* Oncogene Proteins / genetics Oncogene Proteins / metabolism Pancreatic Neoplasms / drug therapy Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology Patched Receptors Patched-1 Receptor Pentacyclic Triterpenes Phenols / chemistry Phenols / pharmacology Phenylethyl Alcohol / analogs & derivatives Phenylethyl Alcohol / chemistry Phenylethyl Alcohol / pharmacology Plant Extracts / pharmacology* Prostatic Neoplasms / drug therapy Prostatic Neoplasms / metabolism Prostatic Neoplasms / pathology Proto-Oncogene Proteins c-bcl-2 / genetics Proto-Oncogene Proteins c-bcl-2 / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Receptors, Cell Surface / antagonists & inhibitors* Receptors, Cell Surface / genetics Receptors, Cell Surface / metabolism Reverse Transcriptase Polymerase Chain Reaction Trans-Activators / antagonists & inhibitors* Trans-Activators / genetics Trans-Activators / metabolism Transcription, Genetic / drug effects* Triterpenes / chemistry Triterpenes / pharmacology Zinc Finger Protein GLI1 Zinc Fingers Ziziphus / chemistry* |
| IF | 3.073 |
| 引用数 | 47 |
| 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) |