Iron(III)-salen damages DNA and induces apoptosis in human cell via mitochondrial pathway

We synthesized a water soluble Fe(III)-salen complex and investigated its biochemical effects on DNA in vitro and on cultured human cells. We showed that Fe(III)-salen produces free radicals in the presence of reducing agent dithiothreitol (DTT) and induces DNA damage in vitro. Interestingly, upon treatment with Fe(III)-salen at concentration as low as 10microM, HEK293 human cells showed morphological changes, nuclear fragmentation, and nuclear condensation that are typical features of apoptotic cell death. The cytotoxicity measurement showed that IC(50) of Fe(III)-salen is 2.0microM for HEK293 cells. Furthermore, treatment with Fe(III)-salen resulted in translocation of cytochrome c from mitochondria to cytosol affecting mitochondrial membrane permeability. Our results demonstrated that Fe(III)-salen not only damages DNA in vitro, but also induces apoptosis in human cells via mitochondrial pathway.