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Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model
Rudjer Bošković Institute, Division of Molecular Medicine, Bijenička 54, Zagreb 10000, Croatia
Croatian Academy of Sciences and Arts, Zrinski trg 11, Zagreb 10000, Croatia
Department of Medicinal Chemistry, University of Zagreb, Faculty of Pharmacy and Biochemistry, Antuna Kovačića 1, Zagreb 10000, Croatia
Biology Department, Faculty of Science, University of Zagreb, Rooseveltov trg 6, Zagreb 10000, Croatia
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, Zagreb 10000, Croatia
Department of Biotechnology, University of Rijeka, Radmile Matejčić 2, Rijeka 51000, Croatia
* Author to whom correspondence should be addressed.
Received: 18 September 2013; in revised form: 15 October 2013 / Accepted: 31 October 2013 / Published: 4 December 2013
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.
Keywords: colorectal cancer; amino acid hydroxyurea derivatives; HDAC inhibition; anti-proliferative effect
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Šaban, N.; Stepanić, V.; Vučinić, S.; Horvatić, A.; Cindrić, M.; Perković, I.; Zorc, B.; Oršolić, N.; Mintas, M.; Pavelić, K.; Pavelić, S.K. Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model. Int. J. Mol. Sci. 2013, 14, 23654-23671.
Šaban N, Stepanić V, Vučinić S, Horvatić A, Cindrić M, Perković I, Zorc B, Oršolić N, Mintas M, Pavelić K, Pavelić SK. Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model. International Journal of Molecular Sciences. 2013; 14(12):23654-23671.
Šaban, Nina; Stepanić, Višnja; Vučinić, Srđan; Horvatić, Anita; Cindrić, Mario; Perković, Ivana; Zorc, Branka; Oršolić, Nada; Mintas, Mladen; Pavelić, Krešimir; Pavelić, Sandra K. 2013. "Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model." Int. J. Mol. Sci. 14, no. 12: 23654-23671.