94 Manganese(III)-Salens Induce Tumor Selective Apoptosis in Human Cells

Wednesday, November 4, 2009: 3:20 PM
Kohlberg (Camino Real Hotel)
Kasiri Sahba , Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX
Khairul I. Ansari , Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX
James D. Grant , Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX
Getachew A. Woldemariam , Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX
Bishakha Shrestha , Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX
Subhrangsu S. Mandal , Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX
In order to explore the apoptotic and anti-tumor activities of metallo-salens, we synthesized several Mn(III)-salen derivatives 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 three different human cancer and non-cancer cells. 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 11–55 micromolar. For Mn(III)-salen complexes with ethylenediamine bridges, methoxy substituted complexes were more active than the corresponding hydroxy derivatives. However, this correlation does not hold when the bridging group was changed from ethylenediamine to o-phenylenediamine. Most importantly, several Mn(III)-salen derivatives showed preferential cytotoxicity toward malignant breast cells (MCF7) over non-malignant breast and colon epithelial cells, indicating their potential application towards novel anti-tumor therapy.