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.