論文 - 詳細
| RRC ID | 87500 |
|---|---|
| 著者 | Nguyen HH, Maneenet J, Fujii T, Caggiano L, Lewis SE, Awale S. |
| タイトル | Grandifloridin D: A Potent Antiausterity Agent Targeting Pancreatic Cancer Cells via Akt/mTOR and Autophagy Inhibition. |
| ジャーナル | Biol Pharm Bull |
| Abstract |
The hypovascular nature of pancreatic tumors creates a nutrient-scarce, hypoxic microenvironment, yet pancreatic cancer cells adapt by altering their metabolism to thrive under austere conditions-a phenomenon known as "austerity." Targeting this adaptation offers a promising strategy for next-generation therapeutics that selectively impair pancreatic cancer cell viability in nutrient-deprived states without toxicity under nutrient-rich conditions. Here, we evaluated the anti-pancreatic cancer properties of grandifloridin D, a synthetic derivative of (+)-grandifloracin. In vitro antiausterity assays demonstrated that grandifloridin D potently and preferentially reduced the viability of MIA PaCa-2 pancreatic cancer cells under nutrient deprivation at a PC50 concentration of 0.14 μM. Live-cell imaging and ethidium bromide/acridine orange (EB/AO) dual staining confirmed that grandifloridin D induces cell death by disrupting membrane integrity. Under nutrient-rich conditions, grandifloridin D exhibited antimetastatic activity, significantly inhibiting MIA PaCa-2 cell migration in real-time assays and suppressing colony formation and spheroid formation. Western blot analysis revealed that grandifloridin D is a potent inhibitor of the protein kinase B (Akt) and mammalian target of rapamycin (mTOR) signaling pathway while also suppressing the autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3). These results suggest that grandifloridin D is a promising antiausterity agent for pancreatic cancer drug development. |
| 巻・号 | 48(11) |
| ページ | 1784-1793 |
| 公開日 | 2025-1-1 |
| DOI | 10.1248/bpb.b25-00545 |
| PMID | 41260676 |
| MeSH | Antineoplastic Agents* / pharmacology Autophagy* / drug effects Cell Line, Tumor Cell Movement / drug effects Cell Survival / drug effects Humans Pancreatic Neoplasms* / drug therapy Pancreatic Neoplasms* / metabolism Pancreatic Neoplasms* / pathology Proto-Oncogene Proteins c-akt* / antagonists & inhibitors Proto-Oncogene Proteins c-akt* / metabolism Signal Transduction / drug effects TOR Serine-Threonine Kinases* / antagonists & inhibitors TOR Serine-Threonine Kinases* / metabolism |
| IF | 1.863 |
| 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 | Bluesky |
| 各媒体での言及数の合計 | 3 |
| 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 | MIA Paca2(RCB2094) |