Effects of copper-cyclam and copper-cyclam/polymer complexes on heLa cells

Abstract

Cyclam-based ligands and their metal complexes have shown antitumor activity. The aim of this study is to prepare positively charged, water soluble Cu(II)-cyclam and Cu(II)-cyclam/poly(acrylic acid) (PAA) complexes which will be used as a chemotherapic agent. In the first part of the study, cyclam reacted with copper(II) to form Cu(II)-cyclam complex. 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 by fouriertrasnform infrared spectroscopy (FTIR), nuclear magnetic resonance (1H-NMR) and atomic absorption spectrophotometer (AAS). To observe, antitumor effects of Cu(II)-cyclam and Cu(II)-cyclam/PAA complexes to HeLa cell lines, 3-[4,5-Dimetiltiazol-2-]-2-5-diphenyl tetrazolium bromide (MTT) test was performed. DNAs of the HeLa cells were isolated and agarose gel electrophoresis was performed to investigate DNA cleavage. To determine the biocompatibility of the complexes, they were interacted with the human serum and analyzed by SDS-PAGE electrophoresis. 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/ml Cu(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. There were no significant effect of neither Cu(II)-cyclam, nor Cu(II)-cyclam/PAA and PAA on the human serum proteins.