Purified Photoproducts of Merocyanine 540 Trigger Cytochrome C Release and Caspase 8-Dependent Apoptosis in Human Leukemia and Melanoma Cells

摘要: If the interplay between caspase proteases and mitochondria decide fate of cell during apoptosis, they may constitute useful molecular targets for novel drug design. We have shown that photoactivated merocyanine 540 (pMC540) triggers caspase-mediated apoptosis in HL60 leukemia M14 melanoma cells. Because pMC540 is a mixture photoproducts, we set out to purify biologically active component(s) from this investigate their ability directly activate intracellular caspases and/or trigger mitochondrial events associated with apoptosis. Two namely C1 C2, purified characterized by mass spectroscopy nuclear magnetic resonance (NMR) analysis, effectively induced Interestingly, both C2 non–receptor-dependent activation 8, which was responsible downstream 3 death. Both compounds release cytochrome C tumor cells rat liver mitochondria; however, different mechanisms were operative translocation response or C2. C1-induced mediated permeability transition (MPT) pore accompanied decrease transmembrane potential (▵ψ m ), whereas independent MPT opening. These findings do not exclude possibility changes ▵ψ are critical some instances, but support notion be universal step apoptotic process. Thus, identification two anticancer agents effector components pathway could implications development newer chemotherapeutic drugs.