title: Imatinib-induced apoptosis: a possible link to topoisomerase enzyme inhibition.
abstract: OBJECTIVE
  Imatinib is a specific BCR/ABL inhibitor, commonly used for the treatment of chronic myeloid leukaemia (CML), a hematological malignancy resulting from a chromosomal translocation that generates the BCR/ABL fusion protein. Recent studies showed that the imatinib has cytotoxic and apoptotic effects on many BCR/ABL-negative cancers. Numerous compounds with cytotoxic potential exert their functions by interfering with the DNA topoisomerase. In this study, we examined the effects of imatinib on tumour cell-killing in relation to DNA topoisomerase enzyme inhibition.
  
  
  METHODS
  We determined the cytotoxicity by cell proliferation assay (XTT; tetrazolium hydroxide), using the human K562 CML cells, and loss of mitochondrial membrane potential by monitoring the changes in caspase-3 enzyme activity. Type I and II topoisomerase activities were measured by supercoiled plasmid relaxation and minicircle DNA decatenation assays respectively.
  
  
  CONCLUSIONS
  Imatinib-induced apoptosis and inhibited cell proliferation in a dose-dependent manner. We also found that the imatinib was effective in both type I and type II topoisomerase reactions to a varying degree between 94% and 7% for the concentration range of 1 mm-0.02 mm in a dose-dependent manner.
  
  
  CONCLUSIONS
  Our results suggest that the inhibition of topoisomerases may be a significant factor in imatinib-induced apoptosis in CML.
authors.affiliation: Department of Molecular Biology and Genetics, Faculty of Sciences, Izmir Institute of Technology, Izmir, Turkey.
authors.forename: Y
authors.initials: Y
authors.lastname: Baran
authors.forename: S
authors.initials: S
authors.lastname: Zencir
authors.forename: Z
authors.initials: Z
authors.lastname: Cakir
authors.forename: E
authors.initials: E
authors.lastname: Ozturk
authors.forename: Z
authors.initials: Z
authors.lastname: Topcu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000187:drug effects* / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000201:enzymology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D053148:Caspase 3; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II