| ID | JOS-ijms24032282 |
| 著者：名前 | |
| 著者：別形式 | Yuan, Bo / Kikuchi, Hidetomo / Li, Jingmei / Kawabata, Atsushi / Yao, Kozo / Takagi, Norio / Okazaki, Mari |
| 著者：カナ | |
| 著者：所属 | 城西大学大学院薬学研究科薬品作用学研究室 / 城西大学大学院薬学研究科薬物療法学研究室 / 城西大学大学院薬学研究科薬品作用学研究室 / 城西大学大学院薬学研究科薬品作用学研究室 / ソレイジア・ファーマ株式会社事業開発本部 / 東京薬科大学薬学部 / 城西大学大学院薬学研究科薬品作用学研究室 |
| 著者：所属(別形式） | Josai University, Graduate School of Pharmaceutical Sciences, Laboratory of Pharmacology / Josai University, Graduate School of Pharmaceutical Sciences, Laboratory of Pharmacotherapy /Josai University, Graduate School of Pharmaceutical Sciences, Laboratory of Pharmacology / Josai University, Graduate School of Pharmaceutical Sciences, Laboratory of Pharmacology / Solasia Pharma K.K., Product Development Division / Tokyo University of Pharmacy & Life Sciences, School of Pharmacy, Department of Applied Biochemistry / Josai University, Graduate School of Pharmaceutical Sciences, Laboratory of Pharmacology |
| 著者版フラグ | publisher |
| 出版地 | Basel |
| 出版者 | MDPI |
| 冊子ISSN | 16616596 |
| 電子ISSN | 14220067 |
| 掲載誌名 | |
| 巻 | 24 |
| 号 | 3 |
| 刊行年月 | 2023-01 |
| 開始ページ | 1 |
| 終了ページ | 21 |
| コンテンツ作成日 | 2022-12-13 |
| コンテンツ修正日 | 2023-01-16 |
| コンテンツ登録日 | 2023-05-16 |
| 識別番号：DOI | info:doi/10.3390/ijms24032282 |
| 識別番号：DOI（リンク） | |
| PubMed番号 | 36768603 |
| 抄録 | To explore the molecular mechanisms of action underlying the antileukemia activities of darinaparsin, an organic arsenical approved for the treatment of peripheral T–cell lymphoma in Japan, cytotoxicity of darinaparsin was evaluated in leukemia cell lines NB4, U-937, MOLT-4 and HL-60. Darinaparsin was a more potent cytotoxic than sodium arsenite, and induced apoptosis/necrosis in NB4 and HL-60 cells. In NB4 cells exhibiting the highest susceptibility to darinaparsin, apoptosis induction was accompanied by the activation of caspase-8/-9/-3, a substantial decrease in Bid expression, and was suppressed by Boc-D-FMK, a pancaspase inhibitor, suggesting that darinaparsin triggered a convergence of the extrinsic and intrinsic pathways of apoptosis via Bid truncation. A dramatic increase in the expression level of γH2AX, a DNA damage marker, occurred in parallel with G2/M arrest. Activation of p53 and the inhibition of cdc25C/cyclin B1/cdc2 were concomitantly observed in treated cells. Downregulation of c-Myc, along with inactivation of E2F1 associated with the activation of Rb, was observed, suggesting the critical roles of p53 and c-Myc in darinaparsin-mediated G2/M arrest. Trolox, an antioxidative reagent, suppressed the apoptosis induction but failed to correct G2/M arrest, suggesting that oxidative stress primarily contributed to apoptosis induction. Suppression of Notch1 signaling was also confirmed. Our findings provide novel insights into molecular mechanisms underlying the cytotoxicity of darinaparsin and strong rationale for its new clinical application for patients with different types of cancer. |
| キーワード | |
| 注記 | p.21 Article number: 2282 Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
| 言語 | eng |
| 資源タイプ | text |
| ジャンル | |
| フォーマット | application/pdf |
| 権利 | Copyright © 2023 by the authors. |
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| このアイテムを表示する：URI | |
