論文 - 詳細
| RRC ID | 74320 |
|---|---|
| 著者 | Eguchi H, Kimura R, Onuma S, Ito A, Yu Y, Yoshino Y, Matsunaga T, Endo S, Ikari A. |
| タイトル | Elevation of Anticancer Drug Toxicity by Caffeine in Spheroid Model of Human Lung Adenocarcinoma A549 Cells Mediated by Reduction in Claudin-2 and Nrf2 Expression. |
| ジャーナル | Int J Mol Sci |
| Abstract |
Claudin-2 (CLDN2), a component of tight junctions, is abnormally expressed in human lung adenocarcinoma tissue. CLDN2 contributes to chemoresistance in human lung adenocarcinoma-derived A549 cells, and it may be a target for cancer therapy. Here, we found that coffee ingredients, namely caffeine and theobromine, decreased the protein level of CLDN2 in human lung adenocarcinoma-derived A549 cells. In contrast, other components, such as theophylline and chlorogenic acid, had no effect. These results indicate that the 7-methyl group in methylxanthines may play a key role in the reduction in CLDN2 expression. The caffeine-induced reduction in the CLDN2 protein was inhibited by chloroquine, a lysosome inhibitor. In a protein-stability assay using cycloheximide, CLDN2 protein levels decreased faster in caffeine-treated cells than in vehicle-treated cells. These results suggest that caffeine accelerates the lysosomal degradation of CLDN2. The accumulation and cytotoxicity of doxorubicin were dose-dependently increased, which was exaggerated by caffeine but not by theophylline in spheroids. Caffeine decreased nuclear factor-erythroid 2-related factor 2 (Nrf2) levels without affecting hypoxia-inducible factor-1α levels. Furthermore, caffeine decreased the expression of Nrf2-targeted genes. The effects of caffeine on CLDN2 expression and anticancer-drug-induced toxicity were also observed in lung adenocarcinoma RERF-LC-MS cells. We suggest that caffeine enhances doxorubicin-induced toxicity in A549 spheroids mediated by the reduction in CLDN2 and Nrf2 expression. |
| 巻・号 | 23(24) |
| 公開日 | 2022-12-7 |
| DOI | 10.3390/ijms232415447 |
| PII | ijms232415447 |
| PMID | 36555089 |
| PMC | PMC9779108 |
| MeSH | A549 Cells Adenocarcinoma of Lung* / metabolism Antineoplastic Agents* / pharmacology Antineoplastic Agents* / therapeutic use Caffeine / pharmacology Caffeine / therapeutic use Claudin-2 Doxorubicin / pharmacology Doxorubicin / therapeutic use Humans Lung Neoplasms* / genetics NF-E2-Related Factor 2 / genetics Theophylline |
| IF | 4.556 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 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 | A549 |