title: The combined effects of proteasome inhibitor bortezomib with topoisomerase I and II inhibitors on topoisomerase enzymes.
abstract: OBJECTIVE
  DNA topoisomerases are ubiquitous enzymes that regulate conformational changes in DNA topology during essential cellular processes, and, for this reason, have been characterized as the cellular targets of a number of anticancer drugs. Bortezomib is a powerful proteasome inhibitor used in the treatment of hematological malignancies. In this study, we investigated the inhibitory effects of bortezomib on human topoisomerase I and II enzymes both alone and in combination modes with camptothecin and etoposide.
  
  
  METHODS
  The interactions of these drugs with topoisomerase enzymes were evaluated by relaxation assay in cell-free systems. IC50values of the drugs on topoisomerase enzymes were calculated using the S probit analysis program.
  
  
  RESULTS
  Bortezomib showed a very weak inhibition effect on topoisomerase I (IC50= 87.11 mM). On the other hand, it had a strong inhibitory effect on topoisomerase II (IC50= 1.41 mM). Our results indicated that bortezomib is effective not only on proteasome but also on topoisomerase II. In addition, bortezomib possesses an increased synergistic effect when used in combination with camptothecin and etoposide than when used alone.
  
  
  CONCLUSIONS
  The results of this study point out that these data may build a framework for combination studies with bortezomib, camptothecin, and etoposide in the treatment of cancer.
authors.affiliation: Molecular Biology Division, Department of Biology, Faculty of Science and Letters, Aksaray University, Aksaray, Turkey.
authors.forename: Emine
authors.initials: E
authors.lastname: Öksüzoğlu
authors.affiliation: Molecular Biology Division, Department of Biology, Faculty of Science and Letters, Aksaray University, Aksaray, Turkey.
authors.forename: Çiydem
authors.initials: Ç
authors.lastname: Tırınoğlu
authors.affiliation: Molecular Biology Division, Department of Biology, Faculty of Science and Letters, Aksaray University, Aksaray, Turkey.
authors.forename: Barış
authors.initials: B
authors.lastname: Kerimoğlu
mesh_terms: D000970:Antineoplastic Agents; D000069286:Bortezomib / Q000494:pharmacology*; D004264:DNA Topoisomerases, Type I; D006801:Humans; D061988:Proteasome Inhibitors; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
chemical_list: D000970:Antineoplastic Agents; D061988:Proteasome Inhibitors; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D000069286:Bortezomib; D004264:DNA Topoisomerases, Type I
keywords: Bortezomib; DNA topoisomerase inhibitors; anticancer drugs; camptothecin; drug combination; etoposide; proteasome inhibitor