Premium
Hypericin photo‐induced apoptosis involves the tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and activation of caspase‐8
Author(s) -
Schempp Christoph M,
Simon-Haarhaus Birgit,
Termeer Christian C,
Simon Jan C
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02268-2
Subject(s) - jurkat cells , hypericin , apoptosis , fas ligand , chemistry , caspase , caspase 8 , tumor necrosis factor alpha , cytotoxic t cell , cancer research , microbiology and biotechnology , programmed cell death , pharmacology , biology , immunology , biochemistry , t cell , immune system , in vitro
Hypericin (HYP) is a photosensitizing pigment from Hypericum perforatum that displays cytotoxic effects in neoplastic cell lines. Therefore, HYP is presently under consideration as a new anticancer drug in photodynamic therapy. Here, we investigated the mechanism of action of HYP photo‐induced apoptosis of Jurkat cells compared to the cytostatic drug paclitaxel (PXL). Both photoactivated HYP and PXL similarly increased the activity of caspase‐8 and caspase‐3, and drug‐induced apoptosis of Jurkat cells was completely blocked by inhibitors of caspase‐8 (Z‐IETD‐FMK) and caspase‐3 (Z‐DEVD‐FMK). The involvement of death receptors was analyzed using neutralizing monoclonal antibodies against Fas (SM1/23), FasL (NOK‐2) and TNF‐R1 (MAB225), and a polyclonal rabbit anti‐human TNF‐related apoptosis‐inducing ligand (TRAIL) antiserum. TRAIL antibody blocked TRAIL‐induced and HYP photo‐induced, but not 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 photo‐induced apoptosis of Jurkat cells is mediated in part by the TRAIL/TRAIL‐receptor system and subsequent activation of upstream caspases.