title: The induction of oxidative stress in cervix carcinoma cells by levoglucosenone derived 4-S-salicyl derivative and (1-4)-S-thio-disaccharides. Part 4.
abstract: (1-4)-S-thiodisaccharides were shown to kill various cancer cell lines, including cervix, lung, mammary-gland and colon by unknown mechanisms. Here we identified two actions of levoglucosenone derived (1-4)-S-thiodisaccharides against cervix cancer cells: induction of oxidative stress and DNA damage. In consequence, (1-4)-S-thiodisaccharides lowered the cellular GSH level and changed the expression profile of genes encoding key proteins involved with oxidative stress response. We also observed that (1-4)-S-thiodisaccharides induced DNA damage and interfered with the thioredoxin (Trx) system. Both actions, as induced by FPC6, were stronger when dihedral angles of sulfur bridge were set to 110°, 100° and 109°, clearly indicating differences when compared to FPC8. These findings demonstrate that the 1-4-thio bridge of disaccharide is a powerful anticancer pharmacophore, and its potential use needs further studies.
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 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 Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, 84 W. South Street, Wilkes-Barre, USA.
authors.forename: Roman
authors.initials: R
authors.lastname: Bielski
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*; D004187:Disaccharides / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D004187:Disaccharides; C512757:1,6-anhydro-3,4-dideoxyhex-3-enopyran-2-ulose; D005947:Glucose
keywords: (1–4)-S-thiodisaccharides; DNA damage; Functional CARB-pharmacophore; Oxidative stress; Reactive oxygen species