PUBLICATION
A novel phenotype-based approach for systematically screening antiproliferation metallodrugs
- Authors
- Wang, Y.H., Cheng, C.C., Lee, W.J., Chiou, M.L., Pai, C.W., Wen, C.C., Chen, W.L., and Chen, Y.H.
- ID
- ZDB-PUB-090819-4
- Date
- 2009
- Source
- Chemico-biological interactions 182(1): 84-91 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Antineoplastic Agents/pharmacology*
- Apoptosis/drug effects
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/pathology
- Cell Growth Processes/drug effects
- Cell Line, Tumor
- Cisplatin/pharmacology
- Drug Screening Assays, Antitumor/methods*
- Embryo, Nonmammalian/drug effects
- Humans
- Liver Neoplasms/drug therapy
- Liver Neoplasms/pathology
- Microscopy, Fluorescence
- Microscopy, Interference
- NF-kappa B/metabolism
- Organometallic Compounds/pharmacology*
- Phenotype
- Ruthenium/pharmacology*
- Tumor Suppressor Protein p53/metabolism
- Zebrafish
- PubMed
- 19682442 Full text @ Chem. Biol. Interact.
- CTD
- 19682442
Citation
Wang, Y.H., Cheng, C.C., Lee, W.J., Chiou, M.L., Pai, C.W., Wen, C.C., Chen, W.L., and Chen, Y.H. (2009) A novel phenotype-based approach for systematically screening antiproliferation metallodrugs. Chemico-biological interactions. 182(1):84-91.
Abstract
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)OH(2)](ClO(4))(2), [Ru(terpy)(tMen)OH(2)](ClO(4))(2), [Ru(terpy)(Me(4)Phen)OH(2)](ClO(4))(2), and Ru(bpy)(2)Cl(2), 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)(dcbpyH(2))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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping