Abstract
The paper presents a detailed study of the biological effects of two amino acid hydroxyurea derivatives that showed selective antiproliferative effects in vitro on the growth of human tumor cell line SW620. Tested compounds induced cell cycle perturbations and apoptosis. Proteins were identified by proteomics analyses using two-dimensional gel electrophoresis coupled to mass spectrometry, which provided a complete insight into the most probable mechanism of action on the protein level. Molecular targets for tested compounds were analyzed by cheminformatics tools. Zinc-dependent histone deacetylases were identified as potential targets responsible for the observed antiproliferative effect.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acids / chemistry*
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Animals
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Apoptosis / drug effects
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Binding Sites
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Cell Cycle Checkpoints / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Colonic Neoplasms / metabolism
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Colonic Neoplasms / mortality
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Colonic Neoplasms / pathology
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Electrophoresis, Gel, Two-Dimensional
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Histone Deacetylases / chemistry
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Histone Deacetylases / metabolism
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Humans
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Hydroxyurea / analogs & derivatives*
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Hydroxyurea / pharmacology
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Hydroxyurea / therapeutic use
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Male
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Mice
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Mice, Inbred BALB C
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Molecular Docking Simulation
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Protein Structure, Tertiary
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Proteome / analysis
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Substances
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Amino Acids
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Antineoplastic Agents
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Proteome
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Histone Deacetylases
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Hydroxyurea