論文 - 詳細
| RRC ID | 61220 |
|---|---|
| 著者 | Fuwa H, Sato M. |
| タイトル | A Synthetic Analogue of Neopeltolide, 8,9-Dehydroneopeltolide, Is a Potent Anti-Austerity Agent against Starved Tumor Cells. |
| ジャーナル | Mar Drugs |
| Abstract |
Neopeltolide, an antiproliferative marine macrolide, is known to specifically inhibit complex III of the mitochondrial electron transport chain (mETC). However, details of the biological mode-of-action(s) remain largely unknown. This work demonstrates potent cytotoxic activity of synthetic neopeltolide analogue, 8,9-dehydroneopeltolide (8,9-DNP), against starved human pancreatic adenocarcinoma PANC-1 cells and human non-small cell lung adenocarcinoma A549 cells. 8,9-DNP induced rapid dissipation of the mitochondrial membrane potential and depletion of intracellular ATP level in nutrient-deprived medium. Meanwhile, in spite of mTOR inhibition under starvation conditions, impairment of cytoprotective autophagy was observed as the lipidation of LC3-I to form LC3-II and the degradation of p62 were suppressed. Consequently, cells were severely deprived of energy sources and underwent necrotic cell death. The autophagic flux inhibited by 8,9-DNP could be restored by glucose, and this eventually rescued cells from necrotic death. Thus, 8,9-DNP is a potent anti-austerity agent that impairs mitochondrial ATP synthesis and cytoprotective autophagy in starved tumor cells. |
| 巻・号 | 15(10) |
| 公開日 | 2017-10-20 |
| DOI | 10.3390/md15100320 |
| PII | md15100320 |
| PMID | 29053565 |
| PMC | PMC5666428 |
| MeSH | A549 Cells Adenocarcinoma / drug therapy Adenocarcinoma / metabolism Adenosine Triphosphate / metabolism Animals Antineoplastic Agents / pharmacology* Apoptosis / drug effects* Autophagy / drug effects* Humans Macrolides / pharmacology* Membrane Potential, Mitochondrial / drug effects Mitochondria / drug effects* Mitochondria / physiology Necrosis / chemically induced Necrosis / physiopathology Oxazoles / pharmacology* Porifera / chemistry Tumor Hypoxia / physiology Tumor Microenvironment / drug effects Tumor Microenvironment / physiology |
| IF | 4.073 |
| 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 | X(Twitter) |
| 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 | A549(RCB0098) PANC-1(RCB2095) |