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Signaling from Lysosomes Enhances Mitochondria-Mediated Photodynamic Therapy in Cancer Cells.
MedLine Citation:
PMID:  22220628     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In photodynamic therapy (PDT), light activates a photosensitizer added to a tissue, resulting in singlet oxygen formation and cell death. The photosensitizer phthalocyanine 4 (Pc 4) localizes primarily to mitochondrial membranes in cancer cells, resulting in mitochondria-mediated cell death. The aim of this study was to determine how lysosomes contribute to PDT-induced cell killing by mitochondria-targeted photosensitizers such as Pc 4. We monitored cell killing of A431cells after Pc 4-PDT in the presence and absence of bafilomycin, an inhibitor of the vacuolar proton pump of lysosomes and endosomes. Bafilomycin was not toxic by itself but greatly enhanced Pc 4-PDT-induced cell killing. To investigate whether iron loading of lysosomes affects bafilomycin-induced killing, cells were incubated with ammonium ferric citrate (30 μM) for 30 hours prior to PDT. Ammonium ferric citrate enhanced Pc 4 plus bafilomycin-induced cell killing without having toxicity by itself. Iron chelators (desferrioxamine and starch-desferrioxamine) and the inhibitor of the mitochondrial calcium (and ferrous iron) uniporter, Ru360, protected against Pc 4 plus bafilomycin toxicity. These results support the conclusion that chelatable iron stored in the lysosomes enhances the efficacy of bafilomycin-mediated PDT and that lysosomal disruption augments PDT with Pc 4. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology© 2012 The American Society of Photobiology.
Authors:
Shalini Saggu; Hsin-I Hung; Geraldine Quiogue; John J Lemasters; Anna-Liisa Nieminen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-5
Journal Detail:
Title:  Photochemistry and photobiology     Volume:  -     ISSN:  1751-1097     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376425     Medline TA:  Photochem Photobiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.
Affiliation:
Center for Cell Death, Injury & Regeneration, Departments of Pharmaceutical & Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 Center for Cell Death, Injury & Regeneration, Departments of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, SC 29425 Center for Cell Death, Injury & Regeneration, Departments of Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425.
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