In vitro inhibition of topoisomerase IIα by reduced glutathione

Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Acta biochimica Polonica (Impact Factor: 1.15). 01/2011; 58(2):265-7.
Source: PubMed


In most cells, the major intracellular redox buffer is glutathione (GSH) and its disulfide-oxidized (GSSG) form. The GSH/GSSG system maintains the intracellular redox balance and the essential thiol status of proteins by thiol disulfide exchange. Topoisomerases are thiol proteins and are a target of thiol-reactive substances. In this study, the inhibitory effect of physiological concentration of GSH and GSSG on topoisomerase IIα activity in vitro was investigated. GSH (0-10 mM) inhibited topoisomerase IIα in a concentration-dependent manner while GSSG (1-100 µM) had no significant effect. These findings suggest that the GSH/GSSG system could have a potential in vivo role in regulating topoisomerase IIα activity.

9 Reads
  • Source
    • "In healthy cells and tissues, over 90% of total glutathione is in reduced form GSH and less than 10% in disulphide form GSSG (Griffith 1999). An increase in the proportion of GSSG to GSH is considered to indicate oxidative stress (Martínez Sarrasague et al. 2006; Valko et al. 2007; Badjatia et al. 2010; Delwar et al. 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Researchers have recently shown an increased interest in free radicals and their role in the tumor microenvironment. Free radicals are molecules with high instability and reactivity due to the presence of an odd number of electrons in the outermost orbit of their atoms. Free radicals include reactive oxygen and nitrogen species, which are key players in the initiation and progression of tumor cells and enhance their metastatic potential. In fact, they are now considered a hallmark of cancer. However, both reactive species may contribute to improve the outcomes of radiotherapy in cancer patients. Besides, high levels of reactive oxygen species may be indicators of genotoxic damage in non-irradiated normal tissues. The purpose of this article is to review recent research on free radicals and carcinogenesis in order to understand the pathways that contribute to tumor malignancy. This review outlines the involvement of free radicals in relevant cellular events, including their effects on genetic instability through (growth factors and tumor suppressor genes, their enhancement of mitogenic signals, and their participation in cell remodeling, proliferation, senescence, apoptosis, and autophagy processes; the possible relationship between free radicals and inflammation is also explored. This knowledge is crucial for evaluating the relevance of free radicals as therapeutic targets in cancer.
    SpringerPlus 08/2013; 2(1):404. DOI:10.1186/2193-1801-2-404


9 Reads
Available from