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請使用永久網址來引用或連結此文件:
https://tkuir.lib.tku.edu.tw/dspace/handle/987654321/42011
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| 題名: | 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 |
| 貢獻者: | 淡江大學生命科學研究所 |
| 關鍵詞: | Apoptosis;Cisplatin;Fin;Metallodrug;Proliferation;Ruthenium |
| 日期: | 2009-11-10 |
| 上傳時間: | 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 |
| 顯示於類別: | [化學學系暨研究所] 期刊論文
[應用數學與數據科學學系] 期刊論文
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