PhotolonTM, a chlorin e6 derivative, triggers ROS production and light-dependent cell death via necrosis

Abstract

PhotolonTM is a photosensitiser with demonstrated potential as an anti-tumour agent. In this study, an in vitro investigation was performed to determine the mechanism of PhotolonTM-induced cell death. Cell killing was observed in a light-dependent manner and light-activated PhotolonTM resulted in a significant production of reactive oxygen species (ROS), which could be blocked by type I ROS scavengers. Inhibition of ROS production using Trolox prevented PhotolonTM-induced cell death. Lightactivated PhotolonTM caused no increase in caspase-3/7 activity, but a rapid increase in lactate dehydrogenase (LDH) release suggesting a loss of membrane integrity and subsequent cell death by necrosis. We conclude that the mechanism of PhotolonTMinduced cell death involves the induction of ROS via a type I mechanism, which is ultimately responsible for cell killing by necrosis.