title: Fas ligand and TRAIL augment the effect of photodynamic therapy on the induction of apoptosis in JURKAT cells.
abstract: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and Fas ligand (FasL) trigger apoptosis by stimulating the formation of a death inducing signaling complex at the cytoplasmic terminus of their respective receptors. Photodynamic therapy (PDT) is an approved treatment for several types of cancer as well as for age-related macular degeneration and is under investigation for different cancer, ocular, autoimmune and cardiovascular indications. The effect of low dose PDT in combination with TRAIL and FasL on Jurkat lymphoma cell apoptosis was examined. Individually, TRAIL, FasL, and PDT could induce apoptosis in these cells. However, at suboptimal levels of PDT, the number of cells undergoing apoptosis was increased when recombinant FasL and/or TRAIL were added. Additive effects of these treatments were evident for different apoptosis parameters including DNA fragmentation, caspase processing and activity and caspase substrate degradation. Overall, these results provide evidence that PDT-treated cells may be more likely to undergo apoptosis when also exposed to receptor-mediated signals delivered by factors such as TRAIL or FasL. For PDT, immune cell-mediated death receptor ligation may represent a way whereby tumor cells that have withstood the direct effects of photosensitization may be eliminated.
authors.affiliation: QLT Inc, Vancouver, BC, Canada.
authors.forename: D J
authors.initials: DJ
authors.lastname: Granville
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: B M
authors.initials: BM
authors.lastname: McManus
authors.forename: D W
authors.initials: DW
authors.lastname: Hunt
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D010450:Endopeptidases / Q000737:chemistry; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000077362:Verteporfin
chemical_list: D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D017319:Photosensitizing Agents; D011166:Porphyrins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D000077362:Verteporfin; D010450:Endopeptidases; D020169:Caspases