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

Kismali G., Emen F. M., Yesilkaynak T., MERAL Ö., Demirkiran D., Sel T., ...Daha Fazla

European Review for Medical and Pharmacological Sciences, cilt.16, sa.8, ss.1001-1012, 2012 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 16 Sayı: 8
  • Basım Tarihi: 2012
  • Dergi Adı: European Review for Medical and Pharmacological Sciences
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1001-1012
  • Anahtar Kelimeler: Metal halide complexes, Apoptosis, Hepatocellular carcinoma, Cell death, HepG2, THERMAL-DECOMPOSITION, BROMIDE COMPLEXES, COPPER COMPLEX, SOLID-STATE, PALLADIUM(II), THIOSEMICARBAZONE, METHYLPYRIDINES, CASPASES, CHLORIDE, ACID
  • Ankara Üniversitesi Adresli: Evet

Özet

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 dichlorodipyridinepalladium( II) (PdCl 2L 1 2), dichlorodipyridinenickel(II) (NiCl 2L 1 2), dichlorodipyridinecopper(II) (CuCl 2L 1 2), dibromodipyridinecopper(II) (CuBr 2L 1 2) and dichlorobis-(2,4-dimethylpyridine)copper(II) (CuCl 2L 2 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, CuCl 2L 2 2 was estimated the most toxic, NiCl 2L 1 2 the least toxic complex. Treatment of CuCl 2L 2 2 in IC50 doses resulted in a remarkable increase lactate dehydrogenase, it was followed by CuBr 2L 1 2 complex. Picnotic nuclei, anisonucleosis and nuclear condensations in 200 μM concentration of CuCl 2L 2 2 and CuCl 2L 1 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, PdCl 2L 1 2, NiCl 2L 1 2, CuCl 2L 1 2, CuBr 2L 1 2, Cu- Cl 2L 2 2 complexes have antiproliferative action on hepatocellular carcinoma cells. However it would be wrong to interpret this effect as an apoptosis or necrosis exactly.