Baran, YusufZencir, SevilÇakır, ZeynepÖztürk, EsraTopçu, Zeki2017-02-242017-02-242011Baran, Y., Zencir, S., Çakır, Z., Öztürk, E., and Topçu, Z. (2011). Imatinib-induced apoptosis: A possible link to topoisomerase enzyme inhibition. Journal of Clinical Pharmacy and Therapeutics, 36(6), 673-679. doi:10.1111/j.1365-2710.2010.01224.x0269-47270269-4727http://doi.org/10.1111/j.1365-2710.2010.01224.xhttp://hdl.handle.net/11147/4904Summary What is known and 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. Results and Discussion: 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. What is new and Conclusion: Our results suggest that the inhibition of topoisomerases may be a significant factor in imatinib-induced apoptosis in CML.eninfo:eu-repo/semantics/openAccessBCR/ABLApoptosisTopoisomeraseChronic myeloid leukaemiaImatinibArticle2-s2.0-8005505905110.1111/j.1365-2710.2010.01224.x10.1111/j.1365-2710.2010.01224.x