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Proceedings Paper

Determinants of PDT-induced apoptosis
Author(s): David Kessel; Yu Luo; Hyeong-Reh Choi Kim
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Paper Abstract

Photodynamic therapy can initiate cell death by apoptosis or necrosis. Using agents with known patterns of sub-cellular localization, we examined the correlation between sites of photodamage and the mode of cell death, using murine leukemia cells in vitro. Mitochondrial or mitochondrial/lysosomal photodamage caused the rapid release of cytochrome c. This effect was not temperature sensitive, and could be demonstrated immediately after irradiation of photosensitized cells at 10 degrees C. Subsequent warming to 37 degrees C led to a rapid apoptotic response, consistent with the known ability of cytochrome c to trigger the activation of caspase-3. In contrast, lysosomal or lysosomal/membrane photodamage resulted in the release of cathepsins and other proteolytic enzymes. A subsequent incubation at 37 degrees C resulted in mitochondrial degradation, leading to loss of cytochrome c within 30 min. The apoptotic response was both delayed and incomplete, with many dead cells not exhibiting an apoptotic morphology. The latter outcome was traced to photodamage to procaspase-3, an effect not observed with sensitizers that caused mainly mitochondrial photodamage. Studies in a cell-free system demonstrated that agents with lysosomal and/or membrane targets could bring about photoinactivation of caspase-3. These result are consistent with the proposal that photodynamic therapy can both activate and inactivate components of the apoptotic process.

Paper Details

Date Published: 29 March 2000
PDF: 5 pages
Proc. SPIE 3909, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy IX, (29 March 2000); doi: 10.1117/12.379884
Show Author Affiliations
David Kessel, Wayne State Univ. School of Medicine (United States)
Yu Luo, Wayne State Univ. School of Medicine (United States)
Hyeong-Reh Choi Kim, Wayne State Univ. School of Medicine (United States)


Published in SPIE Proceedings Vol. 3909:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy IX
Thomas J. Dougherty, Editor(s)

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