Hypericin photo-induced apoptosis involves the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and activation of caspase-8

Hypericin (HYP) is a photosensitizing pigment from Hypericum perforatum tha t displays cytotoxic effects in neoplastic cell lines, Therefore, HYP is pr esently under consideration as a new anticancer drug in photodynamic therap y, Here, we investigated the mechanism of action of HYP photoinduced apopto sis of Jurkat cells compared to the cytostatic drug paclitaxel (PXL), Both photoactivated HYP and PXL similarly increased the activity of caspase-8 an d caspase-3, and drug-induced apoptosis of Jurkat cells was completely bloc ked by; inhibitors of caspase-8 (Z-IETD-FMK) and caspase-3 (Z-DEVD-FMK), Th e involvement of death receptors was analyzed using neutralizing monoclonal antibodies against Fas (SM1/23), FasL (NOK-2) and TNF-R1 (MAB225), and a p olyclonal rabbit anti-human TNF-related apoptosis-inducing ligand (TRAIL) a ntiserum. TRAIL antibody blocked TRAIL-induced and HYP photo-induced, but n ot PXL-induced apoptosis of Jurkat cells, In contrast, PXL-induced, but not HYP-induced apoptosis was blocked by the SM1/23 and NOK-2 antibodies, Anti -TNF-R1 antibody had no effect, These findings suggest that HYP photoinduce d apoptosis of Jurkat cells is mediated in part by the TRAIL/TRAIL-receptor system and subsequent activation of upstream caspases, (C) 2001 Federation of European Biochemical Societies, Published by Elsevier Science B.V. All rights reserved.