Cell death pathways associated with PDT

David Kessel; John J. Reiners Jr.

doi:10.1117/12.639925

15 February 2006 Cell death pathways associated with PDT

David Kessel, John J. Reiners Jr.

Proceedings Volume 6139, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XV; 613902 (2006) https://doi.org/10.1117/12.639925
Event: SPIE BiOS, 2006, San Jose, California, United States

Abstract

Photodynamic therapy leads to both direct and indirect tumor cell death. The latter also involves the consequences of vascular shut-down and immunologic effects. While these factors are a major factor in tumor eradication, there is usually an element of direct cell killing that can reduce the cell population by as much as 2-3 logs. Necrosis was initially believed to represent the predominant PDT death mechanism. An apoptotic response to PDT was first reported by Oleinick in 1991, using a sensitizer that targets the anti-apoptotic protein Bcl-2. Apoptosis leads to fragmentation of DNA and of cells into apoptotic bodies that are removed by phagocytosis. Inflammatory effects are minimized, and the auto- catalytic elements of the process can amplify the death signal. In this study, we examined consequences of Bcl-2 photodamage by a porphycene sensitizer that targets the ER and causes photodamage to the anti-apoptotic protein Bcl-2. Death patterns after Bcl-2 inactivation by a small-molecular antagonist were also assessed. In addition to apoptosis, we also characterized a hitherto undescribed PDT effect, the initiation of autophagy. Autophagy was initially identified as a cell survival pathway, allowing the recycling of components as nutrients become scarce. We propose that autophagy can also represent both a potential survival pathway after PDT damage to cellular organelles, as well as a cell-death pathway. Recent literature reports indicate that autophagy, as well as apoptosis, can be evoked after down-regulation of Bcl-2, a result consistent with results reported here.

Citation Download Citation

David Kessel and John J. Reiners Jr. "Cell death pathways associated with PDT", Proc. SPIE 6139, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XV, 613902 (15 February 2006); https://doi.org/10.1117/12.639925

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