論文 - 詳細
| RRC ID | 51728 |
|---|---|
| 著者 | Isono T, Chano T, Yonese J, Yuasa T. |
| タイトル | Therapeutic inhibition of mitochondrial function induces cell death in starvation-resistant renal cell carcinomas. |
| ジャーナル | Sci Rep |
| Abstract |
Renal cell carcinomas (RCC) have two types of cells for carbon metabolism and for cell signaling under nutrient-deprivation conditions, namely starvation-resistant and starvation-sensitive cells. Here, we evaluated the mitochondrial characteristics of these cell types and found that the resistant type possessed higher activities for both mitochondrial oxidative phosphorylation and glycolysis than the sensitive types. These higher activities were supported by the stored carbon, lipid and carbohydrate sources, and by a low level of mitochondrial reactive oxygen species (ROS) due to sustained SOD2 expression in the resistant RCC cells. In metastatic RCC cases, higher SOD2 expression was associated with a significantly shorter survival period. We found that treatment with the drugs etomoxir and buformin significantly reduced mitochondrial oxidative phosphorylation and induced cell death under glucose-deprivation conditions in starvation-resistant RCC cells. Our data suggest that inhibitory targeting of mitochondria might offer an effective therapeutic option for metastatic RCC that is resistant to current treatments. |
| 巻・号 | 6 |
| ページ | 25669 |
| 公開日 | 2016-5-9 |
| DOI | 10.1038/srep25669 |
| PII | srep25669 |
| PMID | 27157976 |
| PMC | PMC4860706 |
| MeSH | Acids / metabolism Buformin / pharmacology Buformin / therapeutic use Carcinoma, Renal Cell / drug therapy* Carcinoma, Renal Cell / pathology* Cell Death / drug effects Cell Line, Tumor Epoxy Compounds / pharmacology Epoxy Compounds / therapeutic use Flow Cytometry Glycolysis / drug effects Humans Kidney Neoplasms / drug therapy* Kidney Neoplasms / pathology* Kinetics Lipids / chemistry Mitochondria / drug effects Mitochondria / metabolism* Neoplasm Metastasis Oxidative Phosphorylation / drug effects Oxygen Consumption / drug effects Prognosis Reactive Oxygen Species / metabolism Superoxide Dismutase / metabolism |
| IF | 3.998 |
| 引用数 | 11 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | |
| 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 | MKN74(RCB1002) |