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The oxidative induction of DNA lesions in cancer cells by 5-thio-d-glucose and 6-thio-d-fructopyranose and their genotoxic effects. Part 3
Authors:Anna Czubatka-Bienkowska  Anna Macieja  Joanna Sarnik  Zbigniew J. Witczak  Tomasz Poplawski
Affiliation:1. Department of Molecular Genetics, University of Lodz, Lodz 90-236, Poland;2. Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, 84 W. South Street, Wilkes-Barre, USA
Abstract:Thio-sugars have been described as potent inhibitors of cancer cell growth but the detailed mechanism of action remains unknown. Herein we investigated the mechanism of their anticancer action in the HeLa cell line. We investigated two thio-sugars: 5-thio-d-glucose (FCP1) and 6-thio-β-d-fructopyranose (FCP2). We have observed that FCP1 as well as FCP2 clearly induced oxidative DNA lesions in cancer cells and increased the level of cellular ROS. A spin trap and antioxidants have decreased the level of DNA lesions induced by FCPs. FCPs also induced significant changes in the oxidative-stress gene expression. Therefore, we assume that ROS generation is correlated with the increased NOX5 expression by FCPs. Higher cyto- and genotoxicity of FCPs for HeLa cells in a low glucose environment suggested their role in the glucose metabolism. The data indicates that thio-sugars may become drug alternatives for the cancer treatment but such undertaking needs further studies.
Keywords:Functional CARB-pharmacophore  Oxidative stress  DNA damage
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