Phthalocyanine 4 photodynamic therapy-induced apoptosis of mouse L5178Y-R cells results from a delayed but extensive release of cytochrome c from mitochondria.
Photodynamic therapy (PDT) activates the mitochondrial pathway of apoptosis, for which the release of cytochrome c into the cytosol is considered critical. To further elucidate the role of cytochrome c release in PDT-induced apoptosis, we monitored cytochrome c localization immunocytochemically and related it to nuclear apoptosis of the same cells. When mouse L5178Y-R cells were treated with 300 nM phthalocyanine (Pc) 4 and 0-75 mJ/cm(2) red light, cytochrome c release had a dose response similar to that of clonogenic cell killing, with nearly identical threshold doses. Within individual cells, the release of cytochrome c appeared to be an all-or-none phenomenon. Moreover, it was tightly associated with activation of a caspase-3-like protease and changes in nuclear morphology. Thus, in response to Pc 4-PDT, the release of cytochrome c from mitochondria is a key determinant of apoptotic cell death.
Department of Radiation Oncology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-4942, USA.
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S
Chiu
H H
HH
Evans
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M
Lam
A
A
Nieminen
N L
NL
Oleinick
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003574:Cytochrome c Group / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology*; D007940:Leukemia L5178 / Q000473:pathology*; D051379:Mice; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D013347:Subcellular Fractions / Q000187:drug effects; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D003574:Cytochrome c Group; D007211:Indoles; D017319:Photosensitizing Agents; C107448:phthalocyanine Pc 4; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases