Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model

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...

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Main Authors: Nina Šaban, Višnja Stepanić, Srđan Vučinić, Anita Horvatić, Mario Cindrić, Ivana Perković, Branka Zorc, Nada Oršolić, Mladen Mintas, Krešimir Pavelić, Sandra Kraljević Pavelić
Format: Article
Language:English
Published: MDPI AG 2013-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:http://www.mdpi.com/1422-0067/14/12/23654
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spelling doaj-72bf1b34b9d6496e969db6e2ea9f0ec82020-11-24T21:07:12ZengMDPI AGInternational Journal of Molecular Sciences1422-00672013-12-011412236542367110.3390/ijms141223654ijms141223654Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer ModelNina Šaban0Višnja Stepanić1Srđan Vučinić2Anita Horvatić3Mario Cindrić4Ivana Perković5Branka Zorc6Nada Oršolić7Mladen Mintas8Krešimir Pavelić9Sandra Kraljević Pavelić10Rudjer Bošković Institute, Division of Molecular Medicine, Bijenička 54, Zagreb 10000, CroatiaRudjer Bošković Institute, Division of Molecular Medicine, Bijenička 54, Zagreb 10000, CroatiaCroatian Academy of Sciences and Arts, Zrinski trg 11, Zagreb 10000, CroatiaRudjer Bošković Institute, Division of Molecular Medicine, Bijenička 54, Zagreb 10000, CroatiaRudjer Bošković Institute, Division of Molecular Medicine, Bijenička 54, Zagreb 10000, CroatiaDepartment of Medicinal Chemistry, University of Zagreb, Faculty of Pharmacy and Biochemistry, Antuna Kovačića 1, Zagreb 10000, CroatiaDepartment of Medicinal Chemistry, University of Zagreb, Faculty of Pharmacy and Biochemistry, Antuna Kovačića 1, Zagreb 10000, CroatiaBiology Department, Faculty of Science, University of Zagreb, Rooseveltov trg 6, Zagreb 10000, CroatiaDepartment of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, Zagreb 10000, CroatiaDepartment of Biotechnology, University of Rijeka, Radmile Matejčić 2, Rijeka 51000, CroatiaDepartment of Biotechnology, University of Rijeka, Radmile Matejčić 2, Rijeka 51000, CroatiaThe 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.http://www.mdpi.com/1422-0067/14/12/23654colorectal canceramino acid hydroxyurea derivativesHDAC inhibitionanti-proliferative effect
collection DOAJ
language English
format Article
sources DOAJ
author Nina Šaban
Višnja Stepanić
Srđan Vučinić
Anita Horvatić
Mario Cindrić
Ivana Perković
Branka Zorc
Nada Oršolić
Mladen Mintas
Krešimir Pavelić
Sandra Kraljević Pavelić
spellingShingle Nina Šaban
Višnja Stepanić
Srđan Vučinić
Anita Horvatić
Mario Cindrić
Ivana Perković
Branka Zorc
Nada Oršolić
Mladen Mintas
Krešimir Pavelić
Sandra Kraljević Pavelić
Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model
International Journal of Molecular Sciences
colorectal cancer
amino acid hydroxyurea derivatives
HDAC inhibition
anti-proliferative effect
author_facet Nina Šaban
Višnja Stepanić
Srđan Vučinić
Anita Horvatić
Mario Cindrić
Ivana Perković
Branka Zorc
Nada Oršolić
Mladen Mintas
Krešimir Pavelić
Sandra Kraljević Pavelić
author_sort Nina Šaban
title Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model
title_short Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model
title_full Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model
title_fullStr Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model
title_full_unstemmed Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model
title_sort antitumor mechanisms of amino acid hydroxyurea derivatives in the metastatic colon cancer model
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1422-0067
publishDate 2013-12-01
description 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.
topic colorectal cancer
amino acid hydroxyurea derivatives
HDAC inhibition
anti-proliferative effect
url http://www.mdpi.com/1422-0067/14/12/23654
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