Saban Nina, Stepanić Višnja, Vučinić Srđan, Horvatić Anita, Cindrić Mario, Perković Ivana, Zorc Branka, Oršolić Nada, Mintas Mladen, Pavelić Krešimir, Pavelić Sandra Kraljević
Rudjer Bošković Institute, Division of Molecular Medicine, Bijenička 54, Zagreb 10000, Croatia.
Int J Mol Sci. 2013 Dec 4;14(12):23654-71. doi: 10.3390/ijms141223654.
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.
该论文对两种氨基酸羟基脲衍生物的生物学效应进行了详细研究,这两种衍生物在体外对人肿瘤细胞系SW620的生长表现出选择性抗增殖作用。测试的化合物诱导了细胞周期紊乱和细胞凋亡。通过蛋白质组学分析,利用二维凝胶电泳结合质谱法鉴定蛋白质,这在蛋白质水平上全面深入地了解了最可能的作用机制。通过化学信息学工具分析了测试化合物的分子靶点。锌依赖性组蛋白脱乙酰酶被确定为导致观察到的抗增殖效应的潜在靶点。