Comparison of photodynamic targets in a carcinoma cell line and its mitochondrial DNA-deficient derivative.
The relative contribution, to cell death, of photodynamic damage to respiratory proteins (known targets of photodynamic therapy with many photosensitizers) and other cellular sites was examined. The models were a human ovarian carcinoma cell line 2008, and its mitochondrial DNA-deficient derivative ET3, which lacks several key respiratory protein subunits. Phototoxicity was compared in the two cell lines with photosensitizers that localized to different cellular compartments. Photosensitizers included Victoria Blue BO (VBBO; mitochondria); Photofrin with a short incubation, (plasma membrane) or a long incubation (intracellular membranes including mitochondria); and Nile Blue A (NBA; lysosomes). Photosensitizer content and localization did not differ between the 2008 and ET3 cells. For sensitizers without a primary mitochondrial localization (NBA and Photofrin with a short incubation), there was no significant difference between 2008 and ET3 toxicity. Consistent with a mitochondrial localization of VBBO and independence from respiratory-chain damage, ET3 cells were less susceptible than 2008 to both dark- and light-activated VBBO-mediated damage. Statistical analysis of the data demonstrated minimal photobleaching of VBBO and a significant difference between the phototoxicity curves of ET3 and 2008. For Photofrin with a long incubation, dark- and phototoxicity effects were similar for both cell lines. Inhibition of respiratory enzymes is thus only a minor component of Photofrin-mediated (long incubation) phototoxicity in these cell lines and is overwhelmed by more significant damage elsewhere, whereas it is a major but not the exclusive element of death mediated by VBBO.
Morgan
J
J
Department of Dermatology, Roswell Park Cancer Institute, Buffalo, NY 14222, USA. jamorgan@acsu.buffalo.edu
Potter
W R
WR
Oseroff
A R
AR
D004272:DNA, Mitochondrial / Q000235:genetics*; D017323:Dihematoporphyrin Ether / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007928:Lethal Dose 50; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000009:adverse effects / Q000493:pharmacokinetics; D000644:Quaternary Ammonium Compounds / Q000009:adverse effects / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
D004272:DNA, Mitochondrial; D017319:Photosensitizing Agents; D000644:Quaternary Ammonium Compounds; C084160:Victoria blue BO; D017323:Dihematoporphyrin Ether