A novel phenotype-based approach for systematically screening antiproliferation metallodrugs
學年 98
學期 1
出版（發表）日期 2009-11-10
作品名稱 A novel phenotype-based approach for systematically screening antiproliferation metallodrugs
作品名稱（其他語言）
著者 Wang, Yun-hsin; Cheng, Chien-chung; Lee, Wen-jie; Chiou, Min-lun; Pai, Chiung-wen; Wen, Chi-chung; Chen, Wei-li; Chen, Yau-hung
單位 淡江大學生命科學研究所
出版者 Shannon: Elsevier Ireland Ltd
著錄名稱、卷期、頁數 Chemico-Biological Interactions 182(1), pp.84-91
摘要 Ruthenium (Ru) derivatives have less toxicity and higher water-solubility than cisplatin, giving them great potential as antitumor metallodrugs. In this study, zebrafish were employed as a whole-organism model to screen new Ru compounds for anti-cell proliferation activity. After soaking fish embryos in cisplatin and five Ru derivatives, [Ru(terpy)(bpy)Cl]Cl, [Ru(terpy)(dppz)OH2](ClO4)2, [Ru(terpy)(tMen)OH2](ClO4)2, [Ru(terpy)(Me4Phen)OH2](ClO4)2, and Ru(bpy)2Cl2, only cisplatin and [Ru(terpy)(bpy)Cl]Cl-treated embryos displayed obvious phenotypic effects, such as fin-reduction. After further modification of [Ru(terpy)(bpy)Cl]Cl's main structure and the synthesis of two structurally related compounds, [Ru(terpy)(dcbpyH2)Cl]Cl and [Ru(terpy)(dmbpy)Cl]Cl, only [Ru(terpy)(dmbpy)Cl]Cl exhibited fin-reduction phenotypes. TUNEL assays combined with immunostaining techniques revealed that treatment with cisplatin, [Ru(terpy)(bpy)Cl]Cl, and [Ru(terpy)(dmbpy)Cl]Cl led proliferating fin mesenchymal cells to undergo apoptosis and consequently caused fin-reduction phenotypes. Furthermore, [Ru(terpy)(bpy)Cl]Cl was able to activate the P53-dependent and independent pathways, and induced human hepatoma cells to undergo apoptosis. In summary, it was concluded that the zebrafish model was effective for the screening of phenotype-based antiproliferation metallodrugs.
關鍵字 Apoptosis; Cisplatin; Fin; Metallodrug; Proliferation; Ruthenium
語言 en
ISSN 0009-2797
期刊性質 國外
收錄於 SCI
產學合作
通訊作者 Chen, Yau-hung
審稿制度
國別 NLD
公開徵稿
出版型式 紙本
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