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

FEBS Letters

Simon-Haarhaus, Birgit¹  Termeer, Christian C¹  Schempp, Christoph M¹  Simon, Jan C¹ 

[1] Department of Dermatology, University of Freiburg, Hauptstrasse 7, D-79104 Freiburg, Germany

关键词: Apoptosis;    Caspase;    Death receptor;    Hypericin;    Photosensitization;    HYP;    hypericin;    PXL;    paclitaxel;    TRAIL;    TNF-related apoptosis-inducing ligand;    VIS;    visible light;   

DOI  :  10.1016/S0014-5793(01)02268-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown