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High expression of NAMPT in adult T-cell leukemia/lymphoma and anti-tumor activity of a NAMPT inhibitor
http://hdl.handle.net/10659/00006671
http://hdl.handle.net/10659/00006671f9ddeffa-f615-4715-a497-8bdcc808aab5
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
R-2020-205_oosugi.pdf (2.4 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2020-11-18 | |||||
| タイトル | ||||||
| タイトル | High expression of NAMPT in adult T-cell leukemia/lymphoma and anti-tumor activity of a NAMPT inhibitor | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Adult T-cell leukemia/lymphoma | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Apoptosis | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Cell death | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | NAMPT | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Adult T-cell leukemia/lymphoma | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Apoptosis | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Cell death | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | NAMPT | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
Kozako, Tomohiro
× Kozako, Tomohiro× Aikawa, Akiyoshi× Ohsugi, Takeo× Uchida, Yu-ichiro× Kato, Naho× Sato, Keisuke× Ishitsuka, Kenji× Yoshimitsu, Makoto× Honda, Shin-ichiro |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature T lymphocytes induced by human T-cell leukemia virus-1 and has a poor outcome. New molecular targets for the prevention and treatment of ATL are needed urgently. We previously reported high expression of Sirtuin 1, a nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylase, in primary acute-type ATL cells. NAD+ biosynthesis via nicotinamide phosphoribosyltransferase (NAMPT) modulates Sirtuin 1 activity. Here, we examined the expression and effects of inhibiting NAMPT, a rate-limiting enzyme in NAD+ biosynthesis, in ATL cells. We found that peripheral blood mononuclear cells from patients with acute-type ATL expressed significantly higher levels of NAMPT protein than cells from healthy subjects. FK866, a NAMPT inhibitor, induced apoptosis of freshly isolated ATL cells ex vivo and HTLV-1-infected T-cell lines in vitro, which was accompanied by activation of caspases, DNA fragmentation, and disruption of mitochondrial transmembrane potential. However, a pan-caspase inhibitor failed to prevent this FK866-induced cell death, while FK866 increased the caspase-independent cell death mediator endonuclease G. Intriguingly, FK866 also activated autophagy, as demonstrated by increases in protein levels of autophagosome marker LC3-II. Thus, FK866 simultaneously activated apoptosis and autophagy. Finally, FK866 treatment markedly decreased the growth of human ATL tumor xenografts in immunodeficient mice. We showed that NAMPT is highly expressed in primary ATL cells ex vivo, and that FK866 induces autophagy and caspase-dependent and -independent cell death pathways in vitro and has an anti-tumor activity in vivo. These results suggest a novel therapeutic strategy for patients with this fatal disease. | |||||
| 書誌情報 |
European Journal of Pharmacology 巻 865, p. 172738-1-172738-9, 発行日 2019-12 |
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| ISBN | ||||||
| 識別子タイプ | ISBN | |||||
| 関連識別子 | 0014-2999 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1016/j.ejphar.2019.172738 | |||||
| 権利 | ||||||
| 権利情報 | © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license | |||||
| 権利（URI） | ||||||
| 権利情報 | http://creativecommons.org/licenses/by-nc-nd/4.0/ | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| 出版者 | ||||||
| 出版者 | Elsevier B.V. | |||||
| 資源タイプ | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Article | |||||
