The cell death pathway induced by metal halide complexes of pyridine and derivative ligands in hepatocellular carcinoma cells – necrosis or apoptosis?

G. Kismali, F.M. Emen, T. Yesilkaynak, O. Meral, D. Demirkiran, T. Sel, N. Kulcu

Department of Biochemistry, Ankara University Faculty of Veterinary Medicine, Ankara, Turkey. gorkemkismali@yahoo.com

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• Oncology

BACKGROUND: Drugs designed to restore programmed cell death might be effective against many cancer. It was aimed to study the possible apoptotic-necrotic effects of the pyridine-halide complexes such as dichlorodipyridinepalladium(II) (PdCl2L12), dichlorodipyridinenickel(II) (NiCl2L12), dichlorodipyridinecopper(II) (CuCl2L12), dibromodipyridinecopper(II) (CuBr2L12) and dichlorobis-(2,4-dimethylpyridine)copper(II) (CuCl2L22) in the hepatocarcinoma cells (Hep G2).

METHODS: All complexes were characterized by elemental analysis, 1H-NMR, FT-IR and Far-IR spectroscopy. Apoptotic effects were evaluated by cell viability assay, DNA laddering assay, LDH assay, DAPI nuclear staining and caspase 1-3-9 activity analysis.

RESULTS: According to cell proliferation/viability datas, CuCl2L22 was estimated the most toxic, NiCl2L12 the least toxic complex. Treatment of CuCl2L22 in IC50 doses resulted in a remarkable increase lactate dehydrogenase, it was followed by CuBr2L12 complex. Picnotic nuclei, anisonucleosis and nuclear condensations in 200 µM concentration of CuCl2L22 and CuCl2L12 treated cells were observed with DAPI staining also DNA brakes were also determined with electrophoresis. Caspase 1, 3 and 9 increased activation were not detected.

CONCLUSIONS: The present study results indicate that, PdCl2L12, NiCl2L12, CuCl2L12, CuBr2L12, CuCl2L22 complexes have antiproliferative action on hepatocellular carcinoma cells. However it would be wrong to interpret this effect as an apoptosis or necrosis exactly.

 

 

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