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Anti‐cancer effect of TRAIL in combination with caffeic acid phenethyl ester in human hepatocellular carcinoma SK‐Hep1 cells
Author(s) -
Kim An Keun,
Kim Eun Young
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb102
Subject(s) - caffeic acid phenethyl ester , apoptosis , caspase , cancer cell , annexin , chemistry , survivin , poly adp ribose polymerase , caspase 8 , cancer research , cytotoxicity , fas ligand , tumor necrosis factor alpha , effector , pharmacology , programmed cell death , caffeic acid , microbiology and biotechnology , biochemistry , biology , medicine , in vitro , immunology , cancer , antioxidant , enzyme , polymerase
Tumor necrosis factor‐related apoptosis inducing ligand (TRAIL) has been considered as a promising candidate for cancer therapy since it selectively induces apoptosis in various malignant cells but not in normal cells. However, some cancer cells are resistant to TRAIL. Here, we investigated the sensitizing effect of caffeic acid phenethyl ester (CAPE), a phenolic ingredient of honeybee propolis, on TRAIL‐resistant SK‐Hep1 cells. Combined treatment of TRAIL with CAPE synergistically inhibited cell proliferation, and induced apoptosis, whereas either agent alone induced limited cytotoxicity and apoptosis in SK‐Hep1 cells. The synergistic effect of CAPE and TRAIL combination on SK‐Hep1 apoptosis was examined by annexin V staining and poly (ADP‐ribose) polymerase (PARP) cleavage. Moreover, combination of CAPE and TRAIL resulted in significant activation of effector caspases. Furthermore, z‐VAD‐fmk, a pan‐caspase inhibitor, blocked the enhanced apoptosis induced by the combination of CAPE and TRAIL, suggesting the involvement of caspase‐dependent pathway. CAPE also increased the expression of death receptor 5 (DR5). The enhanced cell death and caspase activiation by co‐treatment with CAPE and TRAIL were markedly reduced by human recombinant DR5/Fc chimera protein. Taken together, our results indicate that CAPE enhances TRAIL‐induced apoptosis by caspase activation through induction of DR5. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010–0010538).