論文 - 詳細
| RRC ID | 64113 |
|---|---|
| 著者 | Shi L, Ito F, Wang Y, Okazaki Y, Tanaka H, Mizuno M, Hori M, Hirayama T, Nagasawa H, Richardson DR, Toyokuni S. |
| タイトル | Non-thermal plasma induces a stress response in mesothelioma cells resulting in increased endocytosis, lysosome biogenesis and autophagy. |
| ジャーナル | Free Radic Biol Med |
| Abstract |
Non-thermal plasma (NTP) is a potential new therapeutic modality for cancer. However, its mechanism of action remains unclear. Herein, we studied the effect of NTP on mesothelioma cells and fibroblasts to understand its anti-proliferative efficacy. Interestingly, NTP demonstrated greater selective anti-proliferative activity against mesothelioma cells relative to fibroblasts than cisplatin, which is used for mesothelioma treatment. The anti-proliferative effect of NTP was enhanced by pre-incubation with the cellular iron donor, ferric ammonium citrate (FAC), and inhibited by iron chelation using desferrioxamine (DFO). Three oxidative stress probes (CM-H2DCFDA, MitoSOX and C11-BODIPY) demonstrated reactive oxygen species (ROS) generation by NTP, which was inhibited by DFO. Moreover, NTP decreased transferrin receptor-1 and increased ferritin-H and -L chain expression that was correlated with decreased iron-regulatory protein expression and RNA-binding activity. This regulation was potentially due to increased intracellular iron in lysosomes, which was demonstrated via the Fe(II)-selective probe, HMRhoNox-M, and was consistent with autophagic-induction. Immunofluorescence using LysoTracker and Pepstatin A probes demonstrated increased cellular lysosome content, which was confirmed by elevated LAMP1 expression. The enhanced lysosomal biogenesis after NTP could be due to the observed increase in fluid-phase endocytosis and early endosome formation. These results suggest NTP acts as a stressor, which results in increased endocytosis, lysosome content and autophagy. In fact, NTP rapidly increased autophagosome formation, as judged by increased LC3B-II expression, which co-localized with LAMP1, indicating autophagolysosome formation. Autophagic-induction by NTP was confirmed using electron microscopy. In summary, NTP acts as a cellular stressor to rapidly induce fluid-phase endocytosis, lysosome biogenesis and autophagy. |
| 巻・号 | 108 |
| ページ | 904-917 |
| 公開日 | 2017-7-1 |
| DOI | 10.1016/j.freeradbiomed.2017.04.368 |
| PII | S0891-5849(17)30571-3 |
| PMID | 28465262 |
| MeSH | Autophagy Cell Line, Tumor Cell Proliferation Cisplatin / pharmacology Cisplatin / therapeutic use Deferoxamine / pharmacology Endocytosis Ferric Compounds / pharmacology Fibroblasts / drug effects Fibroblasts / physiology* Humans Iron / metabolism* Lysosomes / metabolism* Mesothelioma / metabolism Mesothelioma / therapy* Oxidative Stress Plasma Gases / pharmacology* Quaternary Ammonium Compounds / pharmacology Reactive Oxygen Species / metabolism |
| IF | 6.17 |
| 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 | X(Twitter) |
| 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 | IMR-90-SV(RCB1024) Rat-1(RCB1830) |