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Inhibition of endocytic processes by photodynamic therapy
1Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. dhkessel@med.wayne.edu
Background And Objectives:
Recent studies have demonstrated an effect of photodamage on the endocytic pathway involved in recycling of membrane components. Using a series of agents with known sub-cellular targets, we explored the determinants of photodynamic inhibition of endocytic processes in three cell lines: A murine leukemia, a murine hepatoma, and a non-malignant epithelial cell line of human origin.
Study Design/Materials And Methods:
The PI-3 kinase antagonist wortmannin blocks endosomal processing pathway dependent on this enzyme, providing an indication of the "flux" of endocytosis. Microscopic observations were used to assess the effect of photodamage on this pathway. Photosensitizing agents specific for mitochondrial, endoplasmic reticulum (ER), lysosomal, and endosomal photodamage were employed.
Results:
Sub-lethal photodamage directed against endosomes or lysosomes interrupted early steps in this endocytic process in the hepatoma cell line. A mechanism for these effects is proposed. Mitochondrial photodamage could interrupt endocytosis, but at levels that also induced apoptosis. ER photodamage did not affect endocytosis even at lethal levels. Somewhat similar results were obtained with other cell lines, but there were sufficient differences to indicate that the cell phenotype is, in part, a determinant of the endocytic response to PDT.
Conclusions:
PDT is therefore seen to have an effect on endocytic processes. Further work will be needed to delineate the role of these endocytic effects in the array of responses to photodynamic therapy.
Insights
Photodynamic therapy (PDT) can inhibit endocytosis, particularly when targeting endosomes or lysosomes. Cell type influences the response to PDT-induced endocytic pathway disruption.
Area of Science:
- Cell biology
- Photodynamic therapy
- Endocytosis
Background:
- Photodamage affects the endocytic pathway involved in membrane component recycling.
- Understanding photodynamic inhibition of endocytosis requires exploring agents with known subcellular targets.
Purpose of the Study:
- To investigate the determinants of photodynamic inhibition of endocytic processes.
- To examine the effects of photodamage on endocytosis across different cell lines.
Main Methods:
- Utilized wortmannin, a PI-3 kinase antagonist, to assess endocytic flux.
- Employed microscopic observations to evaluate photodamage effects on the endocytic pathway.
- Used photosensitizing agents targeting mitochondria, ER, lysosomes, and endosomes.
Main Results:
- Sub-lethal photodamage to endosomes/lysosomes disrupted early endocytic steps in hepatoma cells.
- Mitochondrial photodamage interrupted endocytosis but also induced apoptosis.
- Endoplasmic reticulum photodamage did not affect endocytosis, even at lethal levels.
- Cell phenotype partially determined the endocytic response to photodynamic therapy.
Conclusions:
- Photodynamic therapy impacts endocytic processes.
- Further research is needed to clarify the role of endocytic effects in photodynamic therapy responses.
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