論文 - 詳細
| RRC ID | 77789 |
|---|---|
| 著者 | Aikawa A, Kozako T, Kato N, Ohsugi T, Honda SI. |
| タイトル | Anti-tumor activity of 5-aminoimidazole-4-carboxamide riboside with AMPK-independent cell death in human adult T-cell leukemia/lymphoma. |
| ジャーナル | Eur J Pharmacol |
| Abstract |
Adult T-cell leukemia/lymphoma (ATL) is an aggressive T cell leukemia/lymphoma caused by human T-cell lymphotropic virus type I (HTLV-1). Acadesine or 5-aminoimidazole-4-carboxamide riboside (AICAR) is an AMP-activated protein kinase (AMPK) activator that was recently shown to have tumor suppressive effects on B cell chronic lymphocytic leukemia, but not ATL. This study evaluated the cytotoxic effects of AICAR on ATL-related cell lines and its anti-tumor activity. Here, we demonstrated that AICAR induced cell death via apoptosis and the mitochondrial membrane depolarization of ATL-related cell lines (S1T, MT-1, and MT-2) but not non-HTLV-1-infected Jurkat cells. However, AICAR did not increase the phosphorylation levels of AMPKα. In addition, AICAR increased the expression of the death receptors (DR) DR4 and DR5, and necroptosis-related proteins including phosphorylated receptor-interacting protein family members and the mixed lineage kinase domain-like protein. Interestingly, HTLV-1 Tax, an HTLV-1-encoded oncogenic factor, did not affect AICAR-induced apoptosis. Furthermore, AICAR inhibited the growth of human ATL tumor xenografts in NOD/SCID/gamma mice in vivo. Together, these results suggest that AICAR induces AMPK-independent cell death in ATL-related cell lines and has anti-tumor activity, indicating that it might be a therapeutic agent for ATL. |
| 巻・号 | 961 |
| ページ | 176180 |
| 公開日 | 2023-12-15 |
| DOI | 10.1016/j.ejphar.2023.176180 |
| PII | S0014-2999(23)00694-5 |
| PMID | 37956732 |
| MeSH | AMP-Activated Protein Kinases / metabolism Adult Animals Apoptosis Human T-lymphotropic virus 1* Humans Leukemia-Lymphoma, Adult T-Cell* / drug therapy Leukemia-Lymphoma, Adult T-Cell* / pathology Mice Mice, Inbred NOD Mice, SCID |
| IF | 3.263 |
| 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 | Jurkat(RCB3052) |