論文 - 詳細
| RRC ID | 56638 |
|---|---|
| 著者 | Ishiguro Y, Kobayashi M, Ideno M, Narumi K, Furugen A, Iseki K. |
| タイトル | Valproate sensitizes human glioblastoma cells to 3-bromopyruvate-induced cytotoxicity. |
| ジャーナル | Int J Pharm |
| Abstract |
Glioblastoma (GBM) is the most common brain tumor; however, no effective treatment for it is available yet. Monocarboxylate transporters, which are highly expressed in GBM, play a role in transporting antitumor agents, such as 3-bromopyruvate (3-BrPA). Valproate, primarily used to treat epilepsy, has been considered a possible treatment option for malignant GBM. In this study, we aimed to investigate the combined effects of 3-BrPA and valproate on GBM cell growth and elucidate the underlying mechanisms. Valproate enhanced 3-BrPA-induced cell death in T98G cells, used as a GBM model. Multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) mRNA levels significantly increased after valproate treatment. 3-BrPA-induced cell death, which was enhanced by valproate, was inhibited in the presence of MK571, a MRP inhibitor, or Ko143, a BCRP inhibitor. In addition, treatment with 3-BrPA and valproate for 48 h reduced cellular ATP levels compared to those in the 3-BrPA alone treatment group. However, cellular ATP levels were recovered in the presence of MK571 or Ko143, compared to those in the 3-BrPA and valproate treatment groups. In conclusion, we suggested that valproate enhanced 3-BrPA-induced cell death. This might be attributable to the increase in cellular ATP consumption owing to valproate-induced MRP2 or BCRP expression. |
| 巻・号 | 551(1-2) |
| ページ | 97-102 |
| 公開日 | 2018-11-15 |
| DOI | 10.1016/j.ijpharm.2018.08.039 |
| PII | S0378-5173(18)30617-3 |
| PMID | 30138705 |
| MeSH | ATP-Binding Cassette Transporters / genetics Adenosine Triphosphate / metabolism Antineoplastic Agents / administration & dosage* Brain Neoplasms / drug therapy* Brain Neoplasms / metabolism Cell Line, Tumor Cell Survival / drug effects Glioblastoma / drug therapy* Glioblastoma / metabolism Humans Pyruvates / administration & dosage* RNA, Messenger / metabolism Valproic Acid / administration & dosage* |
| IF | 4.213 |
| 引用数 | 3 |
| 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 | T98G(RCB1954) |