The synthesis and chemical characterization of the novel 2,6-diacetylpyridine-bis(selenosemicarbazone) metal
complexes of Zn(II), Cd(II) and Ni(II) were published previously. Here we report first evidence on anti-proliferative activity
of the complexes and molecular patterns that underlie it. The complexes and the corresponding ligand are shown to be
cytotoxic on the panel of nine, malignant and non-malignant cell lines, with the exception of Ni(II) complex that did not
achieve IC50 value on any of the cell lines tested. Further experiments on the selected cell lines including A 549, MRC-5,
EA.hy 926 and HeLa, have shown that the complexes posses unambiguous property of inducing necrosis in the cells
treated for 6 hours, with the ligand and Zn(II) complex being the most active on all cell lines. On the contrary, only small
portion of early apoptotic events was detected, under the same experimental condition. This was in complete concordance
with the results obtained from Western blot analysis of the treated cells that showed no or slight increase of the protein
amounts of two crucial apoptotic mediators: Cytochrome C and Caspase III. We propose the model, under which tested
complexes induce necroptosis in treated cells, a recently described type of cell death with necrotic morphological features
and acting via caspase independent pathway, and without elevated amounts of intracellular ROS. Endothelial EA.hy 926
cells have proven to be extremely sensitive on the necrosis-inducing effect of the complexes, which could indicate potential
anti-angiogenic effect of the novel complexes that is to be investigated.
Keywords: A 549, EA.hy 926, metal complexes, necroptosis, ROS, selenosemicarbazone, zinc (II) complex.
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