論文 - 詳細
| RRC ID | 68495 |
|---|---|
| 著者 | Sekine K, Fujii H, Abe F. |
| タイトル | Induction of apoptosis by bestatin (ubenimex) in human leukemic cell lines. |
| ジャーナル | Leukemia |
| Abstract |
We investigated the growth inhibitory activity of bestatin, an inhibitor of aminopeptidase N (CD13), on six human leukemic cell lines. Proliferation of all the cell lines except KG1 was inhibited by bestatin. P39/TSU, HL60 and U937 were highly sensitive, with 50% growth inhibitory concentrations (IC50) close to the maximum serum concentration when bestatin was orally administered at 30 mg in clinical application. All cell lines except for K562 highly expressed CD13, but a clear correlation between the sensitivity to bestatin and expression of CD13 was not observed. Other aminopeptidase inhibitors such as amastatin A, arphamenine B and WM15 antibody showed no growth inhibitory effects. To confirm the growth inhibitory effects of bestatin, we quantitatively examined DNA fragmentation in five bestatin-sensitive cell lines. Bestatin dose-dependently induced DNA fragmentation in those cell lines. In case of U937, bestatin induced DNA fragmentation quantitatively and DNA ladder and enhanced caspase-3 activity. Furthermore, the growth inhibition by bestatin was reduced by the caspase inhibitor Z-Asp-CH2-DCB. These results suggested that bestatin exhibits direct antileukemic effects against human leukemic cell lines through the induction of apoptosis. |
| 巻・号 | 13(5) |
| ページ | 729-34 |
| 公開日 | 1999-5-1 |
| DOI | 10.1038/sj.leu.2401388 |
| PMID | 10374877 |
| MeSH | Aminopeptidases / antagonists & inhibitors* Apoptosis / drug effects* CD13 Antigens / analysis Caspase 3 Caspases / physiology Cell Division / drug effects DNA Fragmentation / drug effects Dose-Response Relationship, Drug Humans Leucine / analogs & derivatives* Leucine / pharmacology Leukemia / drug therapy* Leukemia / pathology Protease Inhibitors / pharmacology* Tumor Cells, Cultured |
| IF | 8.665 |
| 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 | Wikipedia |
| 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 | HL60(RCB0041) K562(RCB0027) |