The cell death pathway induced by metal halide complexes of pyridine and derivative ligands in hepatocellular carcinoma cells - necrosis or apoptosis?
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 pyridinehalide complexes such as dichlorodipyridinepalla-dium(ll) (PdCl2L1(2)), dichlorodipyridinenickel(ll) (NiCl2L1(2)), dichlorodipyridinecopper(ll) (CuCl2L1(2)), dibromodipyridinecopper(ll) (CuBr2L1(2)) and dichlorobis-(2,4-dimethylpyridine)copper(ll) (CuCl2L2(2)) 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, CuCl2L2(2) was estimated the most toxic, NiCl2L1(2) the least toxic complex. Treatment of CuCl2L2(2) in IC50 doses resulted in a remarkable increase lactate dehydrogenase, it was followed by CuBr2L1(2) complex. Picnotic nuclei, anisonucleosis and nuclear condensations in 200 microM concentration of CuCl2L2(2) and CuCl2L1(2) 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, PdCl2L1(2), NiCl2L1(2), CuCl2L1(2), CuBr2L1(2), CuC12L2(2) complexes have antiproliferative action on hepatocellular carcinoma cells. However it would be wrong to interpret this effect as an apoptosis or necrosis exactly.
Department of Biochemistry, Ankara University Faculty of Veterinary Medicine, Ankara, Turkey. gorkemkismali@yahoo.com
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020170:Caspase 1 / Q000502:physiology; D053148:Caspase 3 / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D009336:Necrosis; D011725:Pyridines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D011725:Pyridines; D053148:Caspase 3; D020170:Caspase 1