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

Authors
Hee Jung UmJung Hwa OhYoon-Nyun KimYung Hyun ChoiSang Hyun KimJong-Wook ParkTaeg Kyu Kwon
Keimyung Author(s)
박종욱; 권택규; 김윤년
Department
Dept. of Immunology (면역학); Dept. of Internal Medicine (내과학)
Issue Date
2010
Publisher
School of Medicine
Citation
Chemico-biological interactions, Vol.186(1) : 36-42, 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.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/17056
ISSN
0009-2797
Appears in Collections:
1. 연구논문 > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. 연구논문 > 1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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