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
リソース情報
ヒト・動物細胞 T98G(RCB1954)