Effect of Schiff base Cu(II) complexes on signaling pathways in HT-29 cells

Koňariková,Katarína; Perdikaris,Georgios   A.; Gbelcova,Helena; Andrezálová,Lucia; Švéda,Martin; Ruml,Tomáš; Laubertová,Lucia; Žitňanová,Ingrid

doi:10.3892/mmr.2016.5739

Effect of Schiff base Cu(II) complexes on signaling pathways in HT-29 cells

Authors:
- Katarína Koňariková
- Georgios A. Perdikaris
- Helena Gbelcova
- Lucia Andrezálová
- Martin Švéda
- Tomáš Ruml
- Lucia Laubertová
- Ingrid Žitňanová
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Affiliations: Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, 813 72 Bratislava, Slovak Republic, Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, 813 72 Bratislava, Slovak Republic, Department of Biochemistry and Microbiology, Institute of Chemical Technology, Faculty of Food Biochemical Technology, 166 28 Prague, Czech Republic
Published online on: September 14, 2016 https://doi.org/10.3892/mmr.2016.5739
Pages: 4436-4444

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Abstract

Schiff base copper (II) complexes are known for their anticancer, antifungal, antiviral and anti‑inflammatory activities. The aim of the current study was to investigate biological effects of Schiff base Cu (II) complexes (0.001‑100 µmol/l)‑[Cu2(sal‑D, L‑glu)2(isoquinoline)2]·2C2H5OH (1), [Cu(sal‑5‑met‑L‑glu)(H2O)].H2O (2), [Cu(ethanol)2(imidazole)4][Cu2(sal‑D, L-glu)2(imidazole)2] (3), [Cu(sal‑D,L‑glu)(2‑methylimidazole)] (4) on the human colon carcinoma cells HT‑29, the mouse noncancerous cell line NIH‑3T3 and the human noncancerous fibroblast cell line VH10. The results suggested that Cu (II) complexes exhibit cytotoxic effects against the HT‑29 cell line, while complexes 3 and 4 were the most effective. Subsequent to 72 h of incubation, apoptosis was observed in the HT‑29 cells induced by Cu (II) complexes 1 (0.1, 1, 10 and 50 µmol/l), 2 (1, 10, 50 and 100 µmol/l), 3 (0.01, 1, 10 and 50 µmol/l) and 4 (0.01, 0.1, 1 and 10 µmol/l). The apoptotic pathways activated by the Cu (II) complexes were identified. The results indicated that complexes 2, 3 and 4 were able to induce the mitochondria‑dependent pathway of apoptosis in HT‑29 cells, while complex 1 was obsered to activate the extrinsic pathway of apoptosis. The levels of the anti‑apoptotic protein Bcl‑2 were reduced and those of the pro‑apoptotic protein Bax increased following treatment with complexes 2, 3 and 4. Complex 1 had no effect on Bax protein expression. Complexes 2 and 3 induced elevation of cytochrome c (cyt c), while complex 4 induced a time‑dependent elevation of cyt c levels. No cyt c was detected in HT‑29 cells exposed to complex 1, suggesting that Cu (II) complexes activated the extrinsic pathway of apoptosis. The results from the current study in addition to previous studies suggest that Schiff base Cu (II) complexes have potential as novel anticancer drugs.

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