The purpose of this study was to determine the source of reactive oxygen sp
ecies (ROS) generation and the contribution of ROS to the apoptosis of RAW2
64.7 cells induced by cationic liposomes. Cationic liposome-induced apoptos
is was inhibited by lipoxygenase inhibitors, but not inhibitors of NADPH-ox
idase, xanthine oxidase or cyclooxygenase. ROS generation induced by cation
ic liposomes was also inhibited by the lipoxygenase inhibitor NDGA. Further
more, lipid peroxidation was observed following liposome treatment, but the
apoptosis was not inhibited by the antioxidant alpha -tocopherol. These fi
ndings suggested that lipoxygenase is responsible for ROS generation, and R
OS but not lipid peroxidation acts as a key mediator in the progress of apo
ptosis induced by cationic liposomes. (C) 2001 Academic Press.