title: Photolon, a chlorin e6 derivative, triggers ROS production and light-dependent cell death via necrosis.
abstract: 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.
authors.affiliation: Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town 7925, South Africa.
authors.forename: Louise
authors.initials: L
authors.lastname: Copley
authors.forename: Pauline
authors.initials: P
authors.lastname: van der Watt
authors.forename: Karel W
authors.initials: KW
authors.lastname: Wirtz
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Parker
authors.forename: Virna D
authors.initials: VD
authors.lastname: Leaner
mesh_terms: D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002735:Chlorophyllides; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008027:Light; D009336:Necrosis / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D010778:Photochemotherapy / Q000379:methods; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011205:Povidone; D011524:Protoporphyrins / Q000494:pharmacology / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured