Fe(III)-Salen and Salphen Complexes Induce Caspase Activation and Apoptosis in Human Cells

To explore the apoptotic and antitumor activities of metallo-salens, the authors have synthesized several Fe(III)-salen and salphen complexes and analyzed their effects on human cancer and noncancer cells. Their results demonstrated that Fe(III)salen and salphen complexes affect cell viability and induce nuclear fragmentation and apoptosis in breast cancer (MCF7) cells. The IC50 values for the active metallo-salen complexes ranged between 0.3 and 22 mu M in MCF7 cells. Biochemically active Fe(III)-salen and salphen complexes induced caspase-3/7 activation and release of cytochrome c from the mitochondria to cytosol, suggesting the involvement of the mitochondrial pathway of apoptosis. Comparison of IC50 values toward 3 different cell lines demonstrated that selected Fe(III)-salen complexes induce tumor cell-selective apoptosis in cultured cells. Overall, the studies demonstrated that Fe(III)-salen and salphen complexes induced efficient apoptosis in cultured human cells. The nature of the substituents and the bridging spacer between diamino groups play critical roles in determining the apoptotic activities of Fe(III)-salen and salphen complexes. (Journal of Biomolecular Screening 2011:26-35)