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    题名: A novel phenotype-based approach for systematically screening antiproliferation metallodrugs
    作者: Wang, Yun-hsin;Cheng, Chien-chung;Lee, Wen-jie;Chiou, Min-lun;Pai, Chiung-wen;Wen, Chi-chung;Chen, Wei-li;Chen, Yau-hung
    贡献者: 淡江大學生命科學研究所
    关键词: Apoptosis;Cisplatin;Fin;Metallodrug;Proliferation;Ruthenium
    日期: 2009-11-10
    上传时间: 2010-02-23 14:03:13 (UTC+8)
    出版者: Shannon: Elsevier Ireland Ltd
    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.
    關聯: Chemico-Biological Interactions 182(1), pp.84-91
    DOI: 10.1016/j.cbi.2009.08.005
    显示于类别:[化學學系暨研究所] 期刊論文
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