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: Anna Czubatka-Bienkowska, Anna Macieja, Joanna Sarnik, Zbigniew J Witczak, Tomasz Poplawski
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 27 Issue 5 Pg. 1210-1214 (03 01 2017) ISSN: 1464-3405 [Electronic] England
• PMID: 28094181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• Disaccharides
• Fructose
• 5-thio-D-glucose
• 1,6-anhydro-3,4-dideoxyhex-3-enopyran-2-ulose
• Glucose

Topics

• Bridged Bicyclo Compounds, Heterocyclic (chemistry)
• DNA Damage (drug effects)
• Disaccharides (chemistry, pharmacology)
• Female
• Fructose (pharmacology)
• Glucose (analogs & derivatives, chemistry, pharmacology)
• HeLa Cells
• Humans
• Oxidative Stress (drug effects)