論文 - 詳細
| RRC ID | 45146 |
|---|---|
| 著者 | Mitani T, Ito Y, Harada N, Nakano Y, Inui H, Ashida H, Yamaji R. |
| タイトル | Resveratrol reduces the hypoxia-induced resistance to doxorubicin in breast cancer cells. |
| ジャーナル | J Nutr Sci Vitaminol (Tokyo) |
| Abstract |
Resveratrol (3,4',5-trihydroxy-trans-stilbene) is known to enhance the cytotoxicity of the anticancer drug doxorubicin. On the other hand, breast cancer MCF-7 cells acquire resistance to doxorubicin under hypoxic conditions. In this study, we investigated the effect of resveratrol on hypoxia-induced resistance to doxorubicin in MCF-7 cells. Resveratrol and its derivative 3,5-dihydroxy-4'-methoxy-trans-stilbene, but not 3,5-dimethoxy-4'-hydroxy-trans-stilbene, cancelled hypoxia-induced resistance to doxorubicin at a concentration of 10 μM. Carbonyl reductase 1 (CBR1) catalyzes the conversion of doxorubicin to its metabolite doxorubicinol, which is much less effective than doxorubicin. Hypoxia increased the expression of CBR1 at both mRNA and protein levels, and knockdown of CBR1 inhibited hypoxia-induced resistance to doxorubicin in MCF-7 cells. Knockdown of hypoxia-inducible factor (HIF)-1α repressed the hypoxia-induced expression of CBR1. Resveratrol repressed the expression of HIF-1α protein, but not HIF-1α mRNA, and decreased hypoxia-activated HIF-1 activity. Resveratrol repressed the hypoxia-induced expression of CBR1 at both mRNA and protein levels. Likewise, 3,5-dihydroxy-4'-methoxy-trans-stilbene decreased the hypoxia-induced expression of CBR1 protein, but not 3,5-dimethoxy-4'-hydroxy-trans-stilbene. Furthermore, resveratrol decreased the expression of HIF-1α protein even in the presence of the proteasome inhibitor MG132 in hypoxia. Theses results indicate that in MCF-7 cells, HIF-1α-increased CBR1 expression plays an important role in hypoxia-induced resistance to doxorubicin and that resveratrol and 3,5-dihydroxy-4'-methoxy-trans-stilbene decrease CBR1 expression by decreasing HIF-1α protein expression, perhaps through a proteasome-independent pathway, and consequently repress hypoxia-induced resistance to doxorubicin. |
| 巻・号 | 60(2) |
| ページ | 122-8 |
| 公開日 | 2014-1-1 |
| DOI | 10.3177/jnsv.60.122 |
| PII | DN/JST.JSTAGE/jnsv/60.122 |
| PMID | 24975222 |
| MeSH | Alcohol Oxidoreductases / genetics Alcohol Oxidoreductases / metabolism* Antineoplastic Agents / pharmacology Antineoplastic Agents / therapeutic use* Breast Neoplasms / drug therapy* Breast Neoplasms / metabolism Doxorubicin / analogs & derivatives Doxorubicin / pharmacology Doxorubicin / therapeutic use* Drug Resistance, Neoplasm / drug effects* Female Humans Hypoxia Hypoxia-Inducible Factor 1, alpha Subunit / genetics Hypoxia-Inducible Factor 1, alpha Subunit / metabolism* Leupeptins / pharmacology MCF-7 Cells Phytotherapy Plant Extracts / pharmacology Plant Extracts / therapeutic use RNA, Messenger / metabolism Resveratrol Stilbenes / pharmacology Stilbenes / therapeutic use* |
| IF | 1.424 |
| 引用数 | 19 |
| WOS 分野 | NUTRITION & DIETETICS |
| 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 | 3 |
| 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 | MCF7(RCB1904) |