Manganese(III)-salens induce tumor selective apoptosis in human cells

In order to explore the apoptotic and anti-tumor activities of metallo-salens, we synthesized several Mn(III)-salen derivatives (compds. 1-9) and analyzed their effects on cultured human cancer and non-cancer cells. Our results demonstrated that Mn(III)-salen derivatives affect cell viability, induce nuclear condensation and fragmentation in breast cancer cells (MCF7). Mn(III)-salen derivatives also induced caspase-3/7 activation and release of cytochrome-c from the mitochondria to cytosol suggesting that Mn(III)-salen derivatives induce apoptosis in human cells via mitochondrial pathway. Importantly, the nature of the substituent and the bridging spacer between diimino groups on the salen ligand play critical roles in determining the apoptotic activities of Mn(III)-salen derivatives. The IC₅₀ values for the active Mn(III)-salen derivatives lie within the range of 11-40 μM in MCF7 cells. Most importantly, several Mn(III)-salen derivatives showed preferential cytotoxicity (2- to 5-fold) toward malignant breast cells (MCF7) over a non-malignant breast epithelial cell line (MCF10). Notably, the level of cytotoxicity and selectivity of the Mn(III)-salen derivatives towards MCF7 and MCF10 cells are very similar to cisplatin which indicate that Mn(III)-salens are potential novel anti-tumor agent.