Journal
JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
Volume 39, Issue 1, Pages 85-89Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10863-006-9064-8
Keywords
photodynamic therapy; mitochondrial targets; enzyme inhibition; ATP levels; tumor cytotoxicity
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Funding
- NCI NIH HHS [CA26856] Funding Source: Medline
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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 F0F1 ATP synthase. These results were obtained from an in vivo-in vitro experimental pyotocol 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 P-31-NMR spectroscopy of turnors 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.
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