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

Photolon™ 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 Photolon™-induced cell death. Cell killing was observed in a light-dependent manner and light-activated Photolon™ 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 Photolon™-induced cell death. Light-activated Photolon™ 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 Photolon™-induced cell death involves the induction of ROS via a type I mechanism, which is ultimately responsible for cell killing by necrosis.