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BioMed Research International
Volume 2014 (2014), Article ID 765794, 8 pages
Research Article

Heparin and Liver Heparan Sulfate Can Rescue Hepatoma Cells from Topotecan Action

1Department Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
2First Institute of Pathology & Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Üllöi út 26, 1085 Budapest, Hungary
3Department of Otorhinolaryngology, Faculty Medical Department, Asfendiyarov Kazakh National Medical University, Specialty Otorhinolaryngology, Index 05-00-12, Almaty, Kazakhstan

Received 29 May 2014; Revised 23 July 2014; Accepted 12 August 2014; Published 7 September 2014

Academic Editor: George Tzanakakis

Copyright © 2014 József Dudás et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Topotecan (TpT) is a major inhibitory compound of topoisomerase (topo) I that plays important roles in gene transcription and cell division. We have previously reported that heparin and heparan sulfate (HS) might be transported to the cell nucleus and they can interact with topoisomerase I. We hypothesized that heparin and HS might interfere with the action of TpT. To test this hypothesis we isolated topoisomerase I containing cell nuclear protein fractions from normal liver, liver cancer tissues, and hepatoma cell lines. The enzymatic activity of these extracts was measured in the presence of heparin, liver HS, and liver cancer HS. In addition, topo I activity, cell viability, and apoptosis of HepG2 and Hep3B cells were investigated after heparin and TpT treatments. Liver cancer HS inhibited topo I activity in vitro. Heparin treatment abrogated topo I enzyme activity in Hep3B cells, but not in HepG2 cells, where the basal activity was higher. Heparin protected the two hepatoma cell lines from TpT actions and decreased the rate of TpT induced S phase block and cell death. These results suggest that heparin and HS might interfere with the function of TpT in liver and liver cancer.