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Öğe Effects of Gefitinib in the sensitivity of selected Saccharomyces cerevisiae strains(Wiley-Blackwell, 2011) Canturk, P.; Senarisoy, M.; Nitiss, J. L.; Topcu, Z.Öğe Effects of nick formation on DNA substrates via UV-irradiation on the kinetic parameters of mammalian DNA topoisomerase I(Blackwell Publishing, 2006) Kocadag, E.; Sarikaya, D.; Telefoncul, A.; Topcu, Z.Öğe GCN5 participates in ADA3 partnership as revealed with yeast hybrid(Wiley-Blackwell, 2016) Caliskan, G.; Baris, I. C.; Ayaydin, F.; Senarisoy, M.; Boros, I. M.; Topcu, Z.; Zencir, S.Öğe Imatinib-induced apoptosis: a possible link to topoisomerase enzyme inhibition(Wiley-Blackwell, 2011) Baran, Y.; Zencir, S.; Cakir, Z.; Ozturk, E.; Topcu, Z.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.Öğe IMATINIB-INDUCED APOPTOSIS; A POSSIBLE LINK TO TOPOISOMERASE ENZYME INHIBITION(Ferrata Storti Foundation, 2010) Baran, Y.; Zencir, Z.; Cakir, Z.; Ozturk, E.; Topcu, Z.Öğe Inhibitory activities of benzoaxol derivatives on mammalian type I DNA topoisomerase(Blackwell Publishing, 2006) Soyer, Z.; Kocadag, E.; Pabuccuoglu, V.; Telefoncu, A.; Topcu, Z.Öğe Inhibitory activities of Helichrysum taxa on mammalian type I DNA topoisomerase(Taylor & Francis Ltd, 2006) Kucukoglu, O.; Ozturk, B.; Kamataki, T.; Topcu, Z.DNA topoisomerases are essential enzymes that regulate the conformational changes in DNA topology by catalyzing the concerted breakage and rejoining of DNA strands during normal cellular growth. During the past few years, there has been considerable pharmacological interest in these enzymes because the inhibitors of DNA topoisomerases represent a major class of anticancer drugs. In this study, we investigated the effects of the extracts, prepared from a number of Helichrysum taxa, on mammalian DNA topoisomerase I via in vitro supercoil relaxation assays using plasmid substrate, pBR322. Cytotoxic alkaloid, camptothecin, an inhibitor of eukaryotic topoisomerase I, was used as reference compound throughout the assays. Quantitative comparisons of the supercoiled and relaxed DNA band intensities on agarose gels suggested that the extracts from H. pallasii (Sprengel) Ledeb., H. armenium DC subsp. araxinum (Kirp.) Takht, and H. plicatum DC subsp. plicatum manifested a considerable inhibition on the enzyme in a dose-dependent manner. The inhibition of mammalian DNA topoisomerase I by Helichrysum extracts is a significant result because they can be potential sources of anticancer drugs.Öğe Inter-individual variation in CYP2A6 genotypes in relation to lung cancer risk among habitual tobacco smokers in Turkey(Blackwell Publishing, 2006) Zencir, S.; Gumus, N. S.; Lermioglu, F.; Kilic, F.; Goksel, T.; Fujieda, M.; Kamataki, T.; Topcu, Z.Öğe Inter-individual variation of GSTM1 and GSTT1 genotypes in relation to lung cancer risk among habitual tobacco smokers in Turkey(Blackwell Publishing, 2006) Gumus, S. N.; Lermioglu, F.; Goksel, T.; Kamataki, T.; Fujieda, M.; Topcu, Z.Öğe Novel ellipticine derivatives: synthesis and effects on DNA cleavage mediated human topoisomerase II(Wiley-Blackwell, 2016) Kuskucu, M.; Akyildiz, V.; Vann, K. R.; Kalac, A.; Ergun, Y.; Zencir, S.; Osheroff, N.; Topcu, Z.Öğe RT-PCR-based cytochrome P450 expression profile of oral tissue samples(Blackwell Publishing, 2007) Sarikaya, D.; Chiba, I.; Bilgen, C.; Kamatakil, T., I; Topcu, Z.Objective: To analyse the expression of individual forms of cytochrome P450 (CYP) at the mRNA level in five homogenized oral buccal tissue samples from four individuals with or without oral malignancy. Method: Individual forms of CYPs were studied by reverse transcriptase-polymerase chain reaction (RT-PCR), using specific primers for CYPs 2B6, 2C, 2D6, 2E1, 3A3/4 and 3A5, and oral CYP expressions were compared with CYP expression in liver tissue. Results: Consistent expression of CYPs 2C, 2E1 and 3A5 was observed in oral buccal tissue at mRNA level. Conclusions: These particular CYPs have possible roles in the protection of the body against orally ingested xenobiotics as well as influence the bioavailability of therapeutic compounds.Öğe Structural modification of ellipticine derivatives with alkyl groups of varying length is influential on their effects on human DNA topoisomerase II: a combined experimental and computational study(Springer Birkhauser, 2020) Kuskucu, M.; Akyildiz, V.; Kulmany, A.; Ergun, Y.; Zencir, S.; Zupko, I.; Topcu, Z.The compounds reducing tumor cell viability and disrupting DNA topoisomerase reactions have been widely used in anticancer drug development. Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole) is a potent intercalating agent that interferes with nucleic acid processing through interaction with DNA topoisomerase II. Although ellipticine is a well-characterized compound, it is not a widely-accepted drug due to the adverse effects detected upon administration. We have previously reported two novel ellipticine derivatives, N-methyl-5-demethyl ellipticine (ET-1) and 2-methyl-N-methyl-5-demethyl ellipticinium iodide (ET-2) as potent compounds targeting DNA topoisomerase II. This study covers an extended synthesis, characterization, and activity data for five new salts of N-methyl 5-demetyl ellipticine (Z-1, Z-2, Z-4, Z-5 and Z-6) having several organic halides and their effects on human topoisomerase II enzymes. Moreover, combined in silico studies were conducted for better understanding of modes of action of studied molecules at the binding pocket of target. Our results showed that three of the derivatives (Z-1, Z-2, and Z-6) have considerable effect on the catalytic activity of human topoisomerase II implying the influence of alkyl groups added to the parental structure of ellipticine.Öğe Telomeric restriction analysis of vascular smooth muscle cells following balloon angioplasty in rabbits(Springer, 2009) Ozsarlak-Sozer, G.; Kerry, Z.; Oran, I.; Gokce, G.; Tosun, M.; Bechard, L.; Reel, B.; Yasa, M.; Lebe, B.; Topcu, Z.G. OZSARLAK-SOZER, Z. KERRY, I. OR-AN, G. GOKCE, M. TOSUN, L. BECHARD, B. REEL, M. YASA, B. LEBE and Z. TOPCU. Telomeric restriction analysis of vascular smooth muscle cells following balloon angioplasty in rabbits. J Physiol Biochem, 65 (3), 243-250, 2009. Intimal hyperplasia due to smooth muscle cell proliferation and migration has been reported to be responsible for the pathogenesis of atherosclerosis and restenosis, manifested following balloon angioplasty. In this study, we employed the balloon angioplasty model to study telomere length regulation in proliferating vascular smooth muscle cells. Our results showed that balloon angioplasty in iliac arteries resulted in intimal hyperplasia due to proliferation of the smooth muscle cells and small size telomeric restrictional fragments were evident in injured arteries.Öğe Telomeric restriction analysis of vascular smooth muscle cells following balloon angioplasty in rabbits(Springer, 2009) Ozsarlak-Sozer, G.; Kerry, Z.; Oran, I.; Gokce, G.; Tosun, M.; Bechard, L.; Reel, B.; Yasa, M.; Lebe, B.; Topcu, Z.G. OZSARLAK-SOZER, Z. KERRY, I. OR-AN, G. GOKCE, M. TOSUN, L. BECHARD, B. REEL, M. YASA, B. LEBE and Z. TOPCU. Telomeric restriction analysis of vascular smooth muscle cells following balloon angioplasty in rabbits. J Physiol Biochem, 65 (3), 243-250, 2009. Intimal hyperplasia due to smooth muscle cell proliferation and migration has been reported to be responsible for the pathogenesis of atherosclerosis and restenosis, manifested following balloon angioplasty. In this study, we employed the balloon angioplasty model to study telomere length regulation in proliferating vascular smooth muscle cells. Our results showed that balloon angioplasty in iliac arteries resulted in intimal hyperplasia due to proliferation of the smooth muscle cells and small size telomeric restrictional fragments were evident in injured arteries.
