論文 - 詳細
| RRC ID | 44825 |
|---|---|
| 著者 | Ueda JY, Athikomkulchai S, Miyatake R, Saiki I, Esumi H, Awale S. |
| タイトル | (+)-Grandifloracin, an antiausterity agent, induces autophagic PANC-1 pancreatic cancer cell death. |
| ジャーナル | Drug Des Devel Ther |
| Abstract |
Human pancreatic tumors are known to be highly resistant to nutrient starvation, and this prolongs their survival in the hypovascular (austere) tumor microenvironment. Agents that retard this tolerance to nutrient starvation represent a novel antiausterity strategy in anticancer drug discovery. (+)-Grandifloracin (GF), isolated from Uvaria dac, has shown preferential toxicity to PANC-1 human pancreatic cancer cells under nutrient starvation, with a PC50 value of 14.5 μM. However, the underlying mechanism is not clear. In this study, GF was found to preferentially induce PANC-1 cell death in a nutrient-deprived medium via hyperactivation of autophagy, as evidenced by a dramatic upregulation of microtubule-associated protein 1 light chain 3. No change was observed in expression of the caspase-3 and Bcl-2 apoptosis marker proteins. GF was also found to strongly inhibit the activation of Akt, a key regulator of cancer cell survival and proliferation. Because pancreatic tumors are highly resistant to current therapies that induce apoptosis, the alternative cell death mechanism exhibited by GF provides a novel therapeutic insight into antiausterity drug candidates. |
| 巻・号 | 8 |
| ページ | 39-47 |
| 公開日 | 2014-1-1 |
| DOI | 10.2147/DDDT.S52168 |
| PII | dddt-8-039 |
| PMID | 24379655 |
| PMC | PMC3872082 |
| MeSH | Apoptosis / drug effects* Autophagy / drug effects* Bridged-Ring Compounds / pharmacology Bridged-Ring Compounds / therapeutic use* Cell Line, Tumor Dose-Response Relationship, Drug Humans Pancreatic Neoplasms / drug therapy* Pancreatic Neoplasms / pathology Proto-Oncogene Proteins c-akt / antagonists & inhibitors TOR Serine-Threonine Kinases / antagonists & inhibitors |
| IF | 3.216 |
| 引用数 | 30 |
| WOS 分野 | CHEMISTRY, MEDICINAL PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | |
| 各媒体での言及数の合計 | 9 |
| 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 | PANC-1(RCB2095) |