城西大学機関リポジトリJURAEnhanced Cytotoxic Effects of Arenite in Combination with Active Bufadienolide Compounds against Human Glioblastoma Cell Line U-87

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Enhanced Cytotoxic Effects of Arenite in Combination with Active Bufadienolide Compounds against Human Glioblastoma Cell Line U-87

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ID	JOS-molecules27196577
著者：名前	袁, 博/李, ショウ美/宮下, 振一/菊地, 秀与/玄, 美燕/松崎, 広和/岩田, 直洋/神内, 伸也/須永, 克佳/坂本, 武史/日比野, 康英/岡崎, 真理
著者：別形式	Yuan, Bo / Li, Jingmei / Miyashita, Shin-Ich / Kikuchi, Hidetomo / Xuan, Meiyan / Matsuzaki, Hirokazu / Iwata, Naohiro / Kamiuchi, Shinya / Sunaga, Katsuyoshi / Sakamoto, Takeshi / Hibino, Yasuhide / Okazaki, Mari
著者：カナ	エン, パク/リ, ショウミ/ミヤシタ, シンイチ/キクチ, ヒデトモ/ゲン, ビエン/マツザキ, ヒロカズ/イワタ, ナオヒロ/カミウチ, シンヤ/スナガ, カツヨシ/サカモト, タケシ/ヒビノ, ヤスヒデ/オカザキ, マリ
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生体防御学研究室 / 産業技術総合研究所（AIST）/ 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医薬品化学研究室 / 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生体防御学研究室 / 城西大学大学院薬学研究科生体防御学研究室 / 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医薬品化学研究室 / 城西大学大学院薬学研究科生体防御学研究室 / 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 Immunobiochemistry / National Institute of Advanced Industrial Science and Technology (AIST) / Josai University, Graduate School of Pharmaceutical Sciences, Laboratory of Pharmacotherapy / Josai University, Graduate School of Pharmaceutical Sciences, Laboratory of Organic and Medicinal Chemistry / Josai University, Graduate School of Pharmaceutical Sciences, Laboratory of Pharmacology / Josai University, Graduate School of Pharmaceutical Sciences, Laboratory of Immunobiochemistry / Josai University, Graduate School of Pharmaceutical Sciences, Laboratory of Immunobiochemistry / Josai University, Graduate School of Pharmaceutical Sciences, Laboratory of Pharmacotherapy / Josai University, Graduate School of Pharmaceutical Sciences, Laboratory of Organic and Medicinal Chemistry / Josai University, Graduate School of Pharmaceutical Sciences, Laboratory of Immunobiochemistry / 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
電子ISSN	14203049
掲載誌名	Molecules
巻	27
号	19
刊行年月	2022-10
開始ページ	1
終了ページ	21
コンテンツ作成日	2022-09-08
コンテンツ修正日	2022-09-29
コンテンツ登録日	2022-12-24
識別番号：DOI	info:doi/10.3390/molecules27196577
識別番号：DOI（リンク）	https://doi.org/10.3390/molecules27196577
PubMed番号	36235115
抄録	The cytotoxicity of a trivalent arsenic derivative (arsenite, AsIII) combined with arenobufagin or gamabufotalin was evaluated in human U-87 glioblastoma cells. Synergistic cytotoxicity with upregulated intracellular arsenic levels was observed, when treated with AsIII combined with arenobufagin instead of gamabufotalin. Apoptosis and the activation of caspase-9/-8/-3 were induced by AsIII and further strengthened by arenobufagin. The magnitude of increase in the activities of caspase-9/-3 was much greater than that of caspase-8, suggesting that the intrinsic pathway played a much more important role in the apoptosis. An increase in the number of necrotic cells, enhanced LDH leakage, and intensified G2/M phase arrest were observed. A remarkable increase in the expression level of γH2AX, a DNA damage marker, was induced by AsIII+arenobufagin. Concomitantly, the activation of autophagy was observed, suggesting that autophagic cell death associated with DNA damage was partially attributed to the cytotoxicity of AsIII+arenobufagin. Suppression of Notch signaling was confirmed in the combined regimen-treated cells, suggesting that inactivation of Jagged1/Notch signaling would probably contribute to the synergistic cytotoxic effect of AsIII+arenobufagin. Given that both AsIII and arenobufagin are capable of penetrating into the blood–brain barrier, our findings may provide fundamental insight into the clinical application of the combined regimen for glioblastoma.
キーワード	arsenite/arenobufagin/gamabufotalin/glioblastoma/DNA damage/cell death/cell cycle arrest/combination therapy/ 亜砒酸/アレノブファジン/ガマブフォタリン/グリオブラストーマ/併用療法
注記	p.21 Article number: 6577 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	01学術雑誌論文 / Journal Article
フォーマット	application/pdf
権利	Copyright © 2022 by the authors.
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このアイテムを表示する：URI	https://libir.josai.ac.jp/il/meta_pub/G0000284repository_JOS-molecules27196577

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