論文 - 詳細
| RRC ID | 69542 |
|---|---|
| 著者 | Sendo K, Seino M, Ohta T, Nagase S. |
| タイトル | Impact of the glutathione synthesis pathway on sulfasalazine-treated endometrial cancer. |
| ジャーナル | Oncotarget |
| Abstract |
Glutathione is an antioxidant that has an important role in chemotherapeutic drug resistance in cancer. Cysteine is synthesized from cystine and is transported into the cell via the xCT antiporter. Another pathway for synthesizing cysteine involves intracellular methionine. We determined whether targeting the xCT represents a promising strategy for the treatment of endometrial cancer and identified factors that predict efficacy of this treatment strategy. In uterine serous carcinoma (USC) cell lines, the combination of cisplatin and the xCT inhibitor, sulfasalazine, significantly inhibited cell growth compared with single-agent cisplatin or sulfasalazine. Sulfasalazine treatment significantly decreased intracellular glutathione levels and induced apoptosis when combined with cisplatin in USC cell lines. On the one hand, the effectiveness of combined cisplatin and sulfasalazine was not evident in endometrioid carcinoma. USC cell lines exhibited increased expression of xCT and decreased expression of cystathionine gamma lyase (CGL), which is an enzyme involved in the synthesis of cysteine from methionine. On the other hand, endometrioid carcinoma cell lines exhibited increased CGL expression or decreased xCT expression. These findings suggest that using a glutathione synthesis pathway-based approach for selecting subjects for sulfasalazine treatment may be an effective strategy for circumventing glutathione-related chemotherapeutic drug resistance in endometrial carcinoma. |
| 巻・号 | 13 |
| ページ | 224-236 |
| 公開日 | 2022-1-1 |
| DOI | 10.18632/oncotarget.28185 |
| PII | 28185 |
| PMID | 35106124 |
| PMC | PMC8794577 |
| MeSH | Amino Acid Transport System y+ / metabolism Antioxidants Antiporters Carcinoma, Endometrioid* Cell Line, Tumor Cisplatin / metabolism Cisplatin / pharmacology Cystathionine gamma-Lyase / metabolism Cysteine / metabolism Cystine / metabolism Female Glutathione / metabolism Humans Methionine Reactive Oxygen Species / metabolism Sulfasalazine* / pharmacology |
| IF | 5.168 |
| 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 | 7 |
| 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 | HHUA(RCB0658) |