ID | JOS-fonc.2021.628914 |
著者:名前 | |
著者:別形式 | Yuan, Bo / Xu, Kang / 嶋田, 亮太 / Li, JingZhe / Hayashi, Hideki / Okazaki, Mari / Takagi, Norio |
著者:カナ | |
著者:所属 | 城西大学薬学部薬学科 / 東京薬科大学応用生化学教室 / 東京薬科大学応用生化学教室 / China Academy of Chinese Medical Sciences, Experimental Research Center, Beijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases / 東京薬科大学応用生化学教室 / 城西大学薬学部薬学科 / 東京薬科大学応用生化学教室 |
著者:所属(別形式) | Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Pharmacology / Tokyo University of Pharmacy & Life Sciences, Department of Applied Biochemistry / Tokyo University of Pharmacy & Life Sciences, Department of Applied Biochemistry / China Academy of Chinese Medical Sciences, Experimental Research Center, Beijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases / Tokyo University of Pharmacy & Life Sciences, Department of Applied Biochemistry / Josai University, Faculty of Pharmaceutical Sciences, Laboratory of Pharmacology / Tokyo University of Pharmacy & Life Sciences, Department of Applied Biochemistry |
著者版フラグ | publisher |
出版地 | Switzerland |
出版者 | Frontiers Media |
電子ISSN | 2234943X |
掲載誌名 | |
巻 | 11 |
刊行年月 | 2021-03 |
開始ページ | 1 |
終了ページ | 14 |
コンテンツ作成日 | 2020-11-16 |
コンテンツ修正日 | 2021-01-29 |
コンテンツ登録日 | 2021-03-30 |
識別番号:DOI | info:doi/10.3389/fonc.2021.628914 |
識別番号:DOI(リンク) | |
抄録 | Glioblastoma is a fatal primary malignant brain tumor, and the 5-year survival rate of treated glioblastoma patients still remains <5%. Considering the sustained development of metastasis, tumor recurrence, and drug resistance, there is an urgent need for the novel therapeutic approaches to combat glioblastoma. Trivalent arsenic derivative (arsenite, AsIII) with remarkable clinical efficacy in leukemia has been shown to exert cytocidal effect against glioblastoma cells. Gamabufotalin, an active bufadienolide compound, also shows selective cytocidal effect against glioblastoma cells, and has been suggested to serve as a promising adjuvant therapeutic agent to potentiate therapeutic effect of conventional anticancer drugs. In order to gain novel insight into therapeutic approaches against glioblastoma, the cytotoxicity of AsIII and gamabufotalin was explored in the human glioblastoma cell lines U-87 and U-251. In comparison with U-251 cells, U-87 cells were highly susceptible to the two drugs, alone or in combination. More importantly, clinically achieved concentrations of AsIII combined with gamabufotalin exhibited synergistic cytotoxicity against U-87 cells, whereas showed much less cytotoxicity to human normal peripheral blood mononuclear cells. G2/M cell cycle arrest was induced by each single drug, and further augmented by their combination in U-87 cells. Downregulation of the expression levels of cdc25C, Cyclin B1, cdc2, and survivin was observed in U-87 cells treated with the combined regimen and occurred in parallel with G2/M arrest. Concomitantly, lactate dehydrogenase leakage was also observed. Intriguingly, SB203580, a specific inhibitor of p38 MAPK, intensified the cytotoxicity of the combined regimen in U-87 cells, whereas wortmannin, a potent autophagy inhibitor, significantly rescued the cells. Collectively, G2/M arrest, necrosis and autophagy appeared to cooperatively contribute to the synergistic cytotoxicity of AsIII and gamabufotalin. Given that p38 MAPK serves an essential role in promoting glioblastoma cell survival, developing a possible strategy composed of AsIII, gamabufotalin, and a p38 MAPK inhibitor may provide novel insight into approaches designed to combat glioblastoma. |
キーワード | |
注記 | Article 628914, This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
言語 | eng |
資源タイプ | text |
ジャンル | |
フォーマット | application/pdf |
権利 | Copyright © 2021 Yuan, Xu, Shimada, Li, Hayashi, Okazaki and Takagi. |
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