title: Antitumor mechanisms of amino Acid hydroxyurea derivatives in the metastatic colon cancer model.
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.
authors.affiliation: Rudjer Bošković Institute, Division of Molecular Medicine, Bijenička 54, Zagreb 10000, Croatia. sandrakp@biotech.uniri.hr.
authors.forename: Nina
authors.initials: N
authors.lastname: Saban
authors.forename: Višnja
authors.initials: V
authors.lastname: Stepanić
authors.forename: Srđan
authors.initials: S
authors.lastname: Vučinić
authors.forename: Anita
authors.initials: A
authors.lastname: Horvatić
authors.forename: Mario
authors.initials: M
authors.lastname: Cindrić
authors.forename: Ivana
authors.initials: I
authors.lastname: Perković
authors.forename: Branka
authors.initials: B
authors.lastname: Zorc
authors.forename: Nada
authors.initials: N
authors.lastname: Oršolić
authors.forename: Mladen
authors.initials: M
authors.lastname: Mintas
authors.forename: Krešimir
authors.initials: K
authors.lastname: Pavelić
authors.forename: Sandra Kraljević
authors.initials: SK
authors.lastname: Pavelić
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000032:analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D020543:Proteome; D006655:Histone Deacetylases; D006918:Hydroxyurea