15 February 2006 Cell death pathways associated with PDT
Author Affiliations +
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.
© (2006) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
David Kessel, David Kessel, John J. Reiners, John J. Reiners, } "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); doi: 10.1117/12.639925; https://doi.org/10.1117/12.639925


PDT: death pathways
Proceedings of SPIE (February 08 2007)
Promotion of PDT efficacy by HA14-1
Proceedings of SPIE (February 07 2008)
Delineating unique cellular responses to PDT
Proceedings of SPIE (April 07 2005)
The role of reactive oxygen species in PDT efficacy
Proceedings of SPIE (February 17 2009)
Biological consequences of PDT: tying up the loose ends
Proceedings of SPIE (February 08 2011)
Pharmacokinetics of Photofrin II distribution in man
Proceedings of SPIE (May 31 1991)

Back to Top