論文 - 詳細
| RRC ID | 43288 |
|---|---|
| 著者 | Tomiyama N, Matzno S, Kitada C, Nishiguchi E, Okamura N, Matsuyama K. |
| タイトル | The possibility of simvastatin as a chemotherapeutic agent for all-trans retinoic acid-resistant promyelocytic leukemia. |
| ジャーナル | Biol Pharm Bull |
| Abstract |
In this study, the authors evaluated the possible use of 3-hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in anti-leukemic chemotherapy. Cytotoxic potency against HL-60 was as follows; simvastatin (SV)>atorvastatin>cerivastatin>fluvastatin. Interestingly, HL-60-R2, an all-trans retinoic acid (ATRA)-resistant HL-60 variant, was twice as sensitive to SV than HL-60. Further studies revealed the particular mechanism of action of SV-induced apoptosis in leukemia. SV directly and rapidly disordered mitochondria with a loss of its membrane potential, reactive oxygen species (ROS) generation and subsequent irreversible damage with cytochrome c leakage and, finally, SV induced apoptosis through caspase-9 activation, whereas several studies have shown that other statins induced apoptosis to leukemia by the depletion of isoprenoids used for the prenylation of small GTPases, which are essential for cellular signal transduction. Our findings suggest that the mitochondrial pathway plays an important role in the higher potency of SV as a new class of agents for anti-leukemic therapy alone and/or in combination with agents. |
| 巻・号 | 31(3) |
| ページ | 369-74 |
| 公開日 | 2008-3-1 |
| DOI | 10.1248/bpb.31.369 |
| PII | JST.JSTAGE/bpb/31.369 |
| PMID | 18310894 |
| MeSH | Antineoplastic Agents / pharmacology* Apoptosis / drug effects Caspase 9 / metabolism Cell Survival / drug effects Cytochromes c / metabolism Dose-Response Relationship, Drug Drug Resistance, Neoplasm / drug effects* Electrophoresis, Agar Gel HL-60 Cells Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology* Leukemia, Promyelocytic, Acute / drug therapy* Membrane Potential, Mitochondrial / drug effects Mitochondria / drug effects Reactive Oxygen Species / metabolism Simvastatin / pharmacology* Tretinoin / pharmacology* |
| IF | 1.863 |
| 引用数 | 14 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| 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 | HL-60-R2(RCB1550) |