論文 - 詳細
| RRC ID | 61111 |
|---|---|
| 著者 | Yasui H, Yamamoto K, Suzuki M, Sakai Y, Bo T, Nagane M, Nishimura E, Yamamori T, Yamasaki T, Yamada KI, Inanami O. |
| タイトル | Lipophilic triphenylphosphonium derivatives enhance radiation-induced cell killing via inhibition of mitochondrial energy metabolism in tumor cells. |
| ジャーナル | Cancer Lett |
| Abstract |
It has recently been reported that radiation enhances mitochondrial energy metabolism in various tumor cell lines. To examine how this radiation-induced alteration in mitochondrial function influences tumor cell viability, various lipophilic triphenylphosphonium (TPP+) cation derivatives and related compounds such as 4-hydroxy-2,2,6,6-tetramethyl-1-oxy-piperidin (Tempol) with TPP+ (named "Mito-") were designed to inhibit the mitochondrial electron transport chain. Mito-(CH2)10-Tempol (M10T) and its derivatives, Mito-(CH2)5-Tempol (M5T), Mito-(CH2)10-Tempol-Methyl (M10T-Me), Mito-C10H21 (M10), and C10H21-Tempol (10T), were prepared. In HeLa human cervical adenocarcinoma cells and A549 human lung carcinoma cells, the fractional uptake of the compound into mitochondria was highest among the TTP+ analogs conjugated with Tempol (M10T, M5T, and 10T). M10T, M10T-Me, and M10 exhibited strong cytotoxicity and enhanced X-irradiation-induced reproductive cell death, while 10T and M5T did not. Furthermore, M10T, M10T-Me, and M10 decreased basal mitochondrial membrane potential and intracellular ATP. M10T treatment inhibited X-ray-induced increases in ATP production. These results indicate that the TPP cation and a long hydrocarbon linker are essential for radiosensitization of tumor cells. The reduction in intracellular ATP by lipophilic TPP+ is partly responsible for the observed radiosensitization. |
| 巻・号 | 390 |
| ページ | 160-167 |
| 公開日 | 2017-4-1 |
| DOI | 10.1016/j.canlet.2017.01.006 |
| PII | S0304-3835(17)30028-9 |
| PMID | 28093283 |
| MeSH | Antineoplastic Agents / pharmacology Antineoplastic Agents / supply & distribution Cell Death / drug effects* Cell Line, Tumor Drug Synergism Energy Metabolism / drug effects HeLa Cells Humans Hydrophobic and Hydrophilic Interactions Mitochondria / drug effects* Mitochondria / metabolism Neoplasms / physiopathology* Neoplasms / radiotherapy Neoplasms / therapy* Organophosphorus Compounds / chemistry Organophosphorus Compounds / pharmacology* |
| IF | 7.36 |
| 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 | 1 |
| 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) HeLa |