Delineating unique cellular responses to PDT

David Kessel

doi:10.1117/12.582180

8 April 2005 Delineating unique cellular responses to PDT (Invited paper)

David Kessel

Proceedings Volume 5689, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIV; (2005) https://doi.org/10.1117/12.582180
Event: SPIE BiOS, 2005, San Jose, CA, United States

Abstract

Photodamage to mitochondria, endoplasmic reticulum (ER) or lysosomes can lead to activation of the apoptotic program, as can exposure of cells to the non-peptidic Bcl-2/Bcl-x_L antagonist HA14-1. Many signaling pathways are evoked by photodynamic therapy (PDT), presumably from oxidative stress effects. To discover which of the latter effects might be unique to PDT, we compared some photodynamic effects with HA14-1 treatment, using murine leukemia L1210 cells in culture. Two photosensitizers were employed: the porphycene CPO and the chlorin NPe6. The former targets the endoplasmic reticulum (ER) and causes Bcl-2 photodamage, while NPe6 targets lysosomes, resulting in protease-induced cleavage and activation of Bid to form the pro-apoptotic product t-Bid. PDT at either target will lead to loss of the mitochondrial membrane potential ΔΨ_m, translocation of cytochrome c to the cytosol and an apoptotic response. Photodynamic effects of CPO or NPe6 led to activation of several 'stress proteins' and intracellular oxidation of the probe dihydrodichlorofluorescein (H₂DCF). All of these effects were mimicked by HA14-1, indicating that these early responses to PDT result from initiation of apoptosis, however achieved. After CPO-catalyzed PDT or HA14-1 treatment, we observed a prompt release of Ca²⁺into the cytosol, but this was insufficient to significantly alter mitochondrial calcium levels. The apoptotic response to HA14-1 or Bcl-2 photodamage was markedly promoted by the protein kinase C (PKC) inhibitor staurosporin (STS). These effects were not observed after photodamage catalyzed by NPe6, indicating that calcium release and PKC interactions are associated with loss of Bcl-2 function, but not Bid activation.

Citation Download Citation

David Kessel "Delineating unique cellular responses to PDT (Invited paper)", Proc. SPIE 5689, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIV, (8 April 2005); https://doi.org/10.1117/12.582180

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