title: Mitochondria are targets of photodynamic therapy.
abstract: Photodynamic Therapy (PDT) is an evolving cancer treatment that depends on three known and variable components: photosensitizer, light and oxygen. Optimization of these variables yields reactive oxygen species, mainly singlet oxygen, that damage cellular components leading to cytotoxicity. Our research has demonstrated that porphyrin sensitizers, in particular, significantly inhibit the inner mitochondrial membrane enzymes cytochrome c oxidase and F(0)F(1) ATP synthase. These results were obtained from an in vivo-in vitro experimental protocol that exposes sensitizers to metabolic and pharmacokinetic events. The resulting inhibition of oxidative phosphorylation was expected to reduce ATP levels, which were quantitated in cells and were confirmed by (31)P-NMR spectroscopy of tumors in situ in animals treated with PDT. Based on these findings, and more recent investigations of apoptosis, there is little doubt that mitochondria are critical targets in the actions of PDT.
authors.affiliation: Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA. russell_hilf@urmc.rochester.edu
authors.forename: Russell
authors.initials: R
authors.lastname: Hilf
mesh_terms: D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D008027:Light; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy*; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D006180:Proton-Translocating ATPases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D003576:Electron Transport Complex IV; D006180:Proton-Translocating ATPases; D010100:Oxygen