論文 - 詳細
| RRC ID | 51297 |
|---|---|
| 著者 | Kadoda K, Moriwaki T, Tsuda M, Sasanuma H, Ishiai M, Takata M, Ide H, Masunaga SI, Takeda S, Tano K. |
| タイトル | Selective cytotoxicity of the anti-diabetic drug, metformin, in glucose-deprived chicken DT40 cells. |
| ジャーナル | PLoS One |
| Abstract |
Metformin is a biguanide drug that is widely used in the treatment of diabetes. Epidemiological studies have indicated that metformin exhibits anti-cancer activity. However, the molecular mechanisms underlying this activity currently remain unclear. We hypothesized that metformin is cytotoxic in a tumor-specific environment such as glucose deprivation and/or low oxygen (O2) tension. We herein demonstrated that metformin was highly cytotoxic under glucose-depleted, but not hypoxic (2% O2) conditions. In order to elucidate the underlying mechanisms of this selective cytotoxicity, we treated exposed DNA repair-deficient chicken DT40 cells with metformin under glucose-depleted conditions and measured cellular sensitivity. Under glucose-depleted conditions, metformin specifically killed fancc and fancl cells that were deficient in FANCC and FANCL proteins, respectively, which are involved in DNA interstrand cross-link repair. An analysis of chromosomal aberrations in mitotic chromosome spreads revealed that a clinically relevant concentration of metformin induced DNA double-strand breaks (DSBs) in fancc and fancl cells under glucose-depleted conditions. In summary, metformin induced DNA damage under glucose-depleted conditions and selectively killed cells. This metformin-mediated selective toxicity may suppress the growth of malignant tumors that are intrinsically deprived of glucose. |
| 巻・号 | 12(9) |
| ページ | e0185141 |
| 公開日 | 2017-9-19 |
| DOI | 10.1371/journal.pone.0185141 |
| PII | PONE-D-17-20406 |
| PMID | 28926637 |
| PMC | PMC5605006 |
| MeSH | Animals Cell Line Cell Survival / drug effects Chickens Chromosome Aberrations / drug effects DNA Breaks, Double-Stranded / drug effects* DNA Repair / drug effects Glucose / chemistry Hypoglycemic Agents / toxicity* Metformin / toxicity* Oxygen / chemistry Oxygen / metabolism |
| IF | 2.74 |
| 引用数 | 2 |
| 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 | 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 | |
| 原核生物(大腸菌) | |