title: 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.
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.
authors.affiliation: Department of Molecular Genetics, University of Lodz, Lodz 90-236, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Czubatka-Bienkowska
authors.affiliation: Department of Molecular Genetics, University of Lodz, Lodz 90-236, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Macieja
authors.affiliation: Department of Molecular Genetics, University of Lodz, Lodz 90-236, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Sarnik
authors.affiliation: Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, 84 W. South Street, Wilkes-Barre, USA. Electronic address: zbigniew.witczak@wilkes.edu.
authors.forename: Zbigniew J
authors.initials: ZJ
authors.lastname: Witczak
authors.affiliation: Department of Molecular Genetics, University of Lodz, Lodz 90-236, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Poplawski
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D004249:DNA Damage / Q000187:drug effects*; D004187:Disaccharides / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005632:Fructose / Q000494:pharmacology*; D005947:Glucose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D004187:Disaccharides; D005632:Fructose; C003002:5-thio-D-glucose; C512757:1,6-anhydro-3,4-dideoxyhex-3-enopyran-2-ulose; D005947:Glucose
keywords: 5-Thio-d-glucose; 6-Thio-d-fructopyranose; DNA damage; Functional CARB-pharmacophore; Oxidative stress