Fas ligand and TRAIL augment the effect of photodynamic therapy on the induction of apoptosis in JURKAT cells

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and Fas lig and (FasL) trigger apoptosis by stimulating the formation of a death induci ng signaling complex at the cytoplasmic terminus of their respective recept ors. Photodynamic therapy (PDT) is an approved treatment for several types of cancer as well as for age-related macular degeneration and is under inve stigation for different cancer, ocular, autoimmune and cardiovascular indic ations. The effect of low dose PDT in combination with TRAIL and FasL on Ju rkat lymphoma cell apoptosis was examined. Individually, TRAIL, FasL, and P DT could induce apoptosis in these cells. However, at suboptimal levels of PDT, the number of cells undergoing apoptosis was increased when recombinan t FasL and/or TRAIL were added. Additive effects of these treatments were e vident for different apoptosis parameters including DNA fragmentation, casp ase processing and activity and caspase substrate degradation. Overall. the se results provide evidence that PDT-treated cells may be more likely to un dergo apoptosis when also exposed to receptor-mediated signals delivered by factors such as TRAIL or FasL. For PDT, immune cell-mediated death recepto r ligation may represent a way whereby tumor cells that have withstood the direct effects of photosensitization may be eliminated. (C) 2001 Elsevier S cience B.V. All rights reserved.