Effects of Copper-Cyclam and Copper-Cyclam/Polymer Complexes on HeLa Cells

Yıl 2008, Cilt: 36 Sayı: 4, 263 - 271, 01.12.2008

Murat Demirbilek Erhan Pişkin

Öz

Cyclam-based ligands and their metal complexes have shown antitumor activity. The aim of this study is to preparepositively charged, water soluble Cu II -cyclam and Cu II -cyclam/poly acrylic acid PAA complexes which will beused as a chemotherapic agent. In the first part of the study, cyclam reacted with copper II to form Cu II -cyclamcomplex. To increase the antitumor activity of Cu II -cyclam complex, the complex was linked to PAA and Cu II cyclam/PAA complex was prepared. The Cu II -cyclam and Cu II -cyclam/PAA complexes were characterized byfouriertrasnform infrared spectroscopy FTIR , nuclear magnetic resonance 1H-NMR and atomic absorptionspectrophotometer AAS . To observe, antitumor effects of Cu II -cyclam and Cu II -cyclam/PAA complexes to HeLacell lines,3-[4,5-Dimetiltiazol-2-]-2-5-diphenyl tetrazolium bromide MTT test was performed. DNAs of the HeLacells were isolated and agarose gel electrophoresis was performed to investigate DNA cleavage. To determine thebiocompatibility of the complexes, they were interacted with the human serum and analyzed by SDS-PAGEelectrophoresis. FTIR and NMR data proved the formation of complexes. The complex prepared with a Cu II cyclam/PAA mol ratio of 1/1 was used in cell culture experiments. According to the MTT test results 100 µg/mlCu II -cyclam and 100 µg/ml Cu II -cyclam/PAA were able to kill 12.4% and 51.4% of the cells in the culture,respectively. It was shown that 250 µg/ml Cu II -cyclam/PAA complex was able to cleave the DNA effectively. Therewere no significant effect of neither Cu II -cyclam, nor Cu II -cyclam/PAA and PAA on the human serum proteins

Anahtar Kelimeler

1, 4, 8, 11-tetra-azacyclotetradecan cyclam, metal-chelate ligand, cancer therapy, HeLa cell lines, PAA

Kaynakça

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