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The coffee diterpene kahweol sensitizes TRAIL-induced apoptosis in renal carcinoma Caki cells through down-regulation of Bcl-2 and c-FLIP

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Author(s)
박종욱권택규김윤년
Alternative Author(s)
Park, Jong WookKwon, Taeg KyuKim, Yoon Nyun
Publication Year
2010
Abstract
Kahweol, a coffee-specific diterpene, found in the beans of Coffea arabica, has potent anti-carcinogenic, anti-tumor, and anti-inflammatory properties. TRAIL is a potential anti-cancer compound that induces apoptosis in a wide variety of cancer cells, but not in most normal human cell types. In the present study, we show that kahweol sensitizes human renal cancer cells, but not normal human mesangial cells, to TRAIL-mediated apoptosis. Moreover, treatment with a combination of kahweol and TRAIL induces significant apoptosis in various cancer cell types, thus presenting an attractive novel strategy for cancer treatment. Our experiments show that treatment with a combination of kahweol and TRAIL-induced apoptosis, and stimulated of DEVDase activity, DNA fragmentation, and cleavage of PARP, which was prevented by pretreatment with z-VAD, indicative of cell death via a caspase-dependent pathway. Kahweol-induced down-regulation of Bcl-2 and ectopic expression of Bcl-2 led to attenuation of kahweol plus TRAIL-mediated apoptosis, indicative of Bcl-2 involvement in the apoptotic process. In addition, the c-FLIP and caspase signal pathways seem to play a crucial role in apoptosis triggered by the combination of kahweol and TRAIL in Caki cells. Our results collectively demonstrate that down-regulation of Bcl-2 and c-FLIP contributes to the sensitizing effect of kahweol on TRAIL-mediated apoptosis in cancer cells.

Keywords
Kahweol;
TRAIL;
Apoptosis;
Caki;
Bcl-2;
c-FLIP
Department
Dept. of Immunology (면역학)
Dept. of Internal Medicine (내과학)
Publisher
School of Medicine
Citation
Chemico-biological interactions, Vol.186(1) : 36-42, 2010
Type
Article
ISSN
0009-2797
DOI
10.1016/j.cbi.2010.04.013
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35395
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