論文 - 詳細
| RRC ID | 41745 |
|---|---|
| 著者 | Yoshida S, Honda A, Matsuzaki Y, Fukushima S, Tanaka N, Takagiwa A, Fujimoto Y, Miyazaki H, Salen G. |
| タイトル | Anti-proliferative action of endogenous dehydroepiandrosterone metabolites on human cancer cell lines. |
| ジャーナル | Steroids |
| Abstract |
Dehydroepiandrosterone (DHEA) is a naturally occurring steroid synthesized in the adrenal cortex, gonads, brain, and gastrointestinal tract, and it is known to have chemopreventive and anti-proliferative actions on tumors. These effects are considered to be induced by the inhibition of glucose-6-phosphate dehydrogenase (G6PD) and/or HMG-CoA reductase (HMGR) activities. The present study was undertaken to investigate whether endogenous DHEA metabolites, i.e. DHEA-sulfate, 7-oxygenated DHEA derivatives, androsterone, epiandrosterone, and etiocholanolone, have anti-proliferative effects on cancer cells and to clarify which enzyme, G6PD or HMGR, is responsible for growth inhibition. Growth of Hep G2, Caco-2, and HT-29 cells, evaluated by 3-[4,5-dimethylthiazol]-2yl-2,5-diphenyl tetrazolium bromide (MTT) and bromodeoxyuridine incorporation assays, was time- and dose-dependently inhibited by addition of all DHEA-related steroids we tested. In particular, the growth inhibition due to etiocholanolone was considerably greater than that caused by DHEA in all cell lines. The suppression of growth of the incubated steroids was not correlated with the inhibition of G6PD (r=-0.031, n=9, NS) or HMGR (r=0.219, n=9, NS) activities. The addition of deoxyribonucleosides or mevalonolactone to the medium did not overcome the inhibition of growth induced by DHEA or etiocholanolone, while growth suppression by DHEA was partially prevented by the addition of ribonucleosides. These results demonstrate that endogenous DHEA metabolites also have an anti-proliferative action that is not induced by inhibiting G6PD or HMGR activity alone. These non-androgenic DHEA metabolites may serve as chemopreventive or anti-proliferative therapies. |
| 巻・号 | 68(1) |
| ページ | 73-83 |
| 公開日 | 2003-1-1 |
| DOI | 10.1016/s0039-128x(02)00117-4 |
| PII | S0039128X02001174 |
| PMID | 12475725 |
| MeSH | Cell Division / drug effects* Dehydroepiandrosterone / analogs & derivatives* Dehydroepiandrosterone / metabolism* Dehydroepiandrosterone / pharmacology* Dehydroepiandrosterone Sulfate / pharmacology Dose-Response Relationship, Drug Etiocholanolone / pharmacology Glucosephosphate Dehydrogenase / drug effects Glucosephosphate Dehydrogenase / metabolism Humans Hydroxymethylglutaryl CoA Reductases / drug effects Hydroxymethylglutaryl CoA Reductases / metabolism Kinetics Neoplasms / drug therapy Neoplasms / pathology* Oxidation-Reduction Ribonucleosides / pharmacology Tumor Cells, Cultured |
| IF | 1.948 |
| 引用数 | 63 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM BIOCHEMISTRY & MOLECULAR BIOLOGY |
| 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 | Patent(IFI CLAIMS) |
| 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 | Hep G2(RCB1648) |