Mechanism of cell death by 5-aminolevulinic acid-based photodynamic action and its enhancement by ferrochelatase inhibitors in human histiocytic lymphoma cell line U937

Photodynamic therapy (PDT) for tumors is based oil the tumor-selective accumulation of a photosensitizer. protoporphyrin IX (PpIX), followed by irradiation with visible light However, the molecular mechanism of cell death caused by PDT has not been fully elucidated The 5-aminolevulinic acid (ALA)-based photodynamic action (PDA) was dependent oil file accumulation of PpIX, the level of which decreased rapidly by eliminating ALA from the incubation medium in human histiocytic lymphoma U937 cells PDA induced apoptosis characterized by lipid peroxidation. increase in Bak and Bax/Bcl-xL, decrease fit Bid. membrane depolarization, cytochrome c release. caspase-3 activation, phosphandylserine (PS) externalization. PDT-induced cell death seemed to occur predominantly via apoptosis through distribution of PpIX in mitochondria These cell death events were enhanced by ferrochelatase inhibitors These results indicated that ALA-based-PDA induced apoptotic cell death through a mitochondrial pathway and that ferrochelatase inhibitors enhanced the effect of PDT for tumors even at low concentrations of ALA. Copyright (C) 2009 John Wiley & Sons. Ltd