title: Heparin and liver heparan sulfate can rescue hepatoma cells from topotecan action.
abstract: 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.
authors.affiliation: Department Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria ; First Institute of Pathology & Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Üllöi út 26, 1085 Budapest, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Dudás
authors.affiliation: First Institute of Pathology & Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Üllöi út 26, 1085 Budapest, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Bocsi
authors.affiliation: First Institute of Pathology & Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Üllöi út 26, 1085 Budapest, Hungary.
authors.forename: Alexandra
authors.identifier: 0000-0003-4368-1523
authors.initials: A
authors.lastname: Fullár
authors.affiliation: First Institute of Pathology & Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Üllöi út 26, 1085 Budapest, Hungary.
authors.forename: Kornélia
authors.identifier: 0000-0002-5323-2775
authors.initials: K
authors.lastname: Baghy
authors.affiliation: First Institute of Pathology & Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Üllöi út 26, 1085 Budapest, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Füle
authors.affiliation: Department Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria ; Department of Otorhinolaryngology, Faculty Medical Department, Asfendiyarov Kazakh National Medical University, Specialty Otorhinolaryngology, Index 05-00-12, Almaty, Kazakhstan.
authors.forename: Saule
authors.initials: S
authors.lastname: Kudaibergenova
authors.affiliation: First Institute of Pathology & Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Üllöi út 26, 1085 Budapest, Hungary.
authors.forename: Ilona
authors.identifier: 0000-0002-0179-3378
authors.initials: I
authors.lastname: Kovalszky
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D056945:Hep G2 Cells; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D006497:Heparan Sulfate / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019772:Topotecan / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D004264:DNA Topoisomerases, Type I; D004273:DNA, Neoplasm; D006493:Heparin; D006497:Heparan Sulfate; D019772:Topotecan; C528909:TOP1 protein, human