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6-Shogaol enhances renal carcinoma Caki cells to TRAIL-induced apoptosis through reactive oxygen species-mediated cytochrome c release and down-regulation of c-FLIP(L) expression

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Author(s)
김신박종욱권택규김동은
Alternative Author(s)
Kim, ShinPark, Jong WookKwon, Taeg KyuKim, Dong Eun
Publication Year
2015
Abstract
6-Shogaol, a potent bioactive compound in ginger (Zingiber officinale Roscoe), has been reported for antiinflammatory and anti-cancer activity. In this study, we investigated the effect of 6-shogaol to enhance tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. The combined treatment with 6-shogaol and TRAIL markedly induces apoptosis in various cancer cells (renal carcinoma Caki cells, breast carcinoma MDA-MB-231 cells and glioma U118MG cells), but not in normal mesangial cells and normal mouse kidney cells. 6-Shogaol reduced the mitochondrial membrane potential (MMP) and released cytochrome c from mitochondria to cytosol via Bax activation. Furthermore, we found that 6-shogaol induced down-regulation of c-FLIP(L) expression at the post-translational levels and the overexpression of c-FLIP(L) markedly inhibited 6-shogaol plus TRAIL-induced apoptosis. Moreover, 6-shogaol increased reactive oxygen species (ROS) production in Caki cells. Pretreatment with ROS scavengers attenuated 6-shogaol plus TRAIL-induced apoptosis through inhibition of MMP reduction and down-regulation of c-FLIP(L) expression. In addition, 6-gingerol, another phenolic alkanone isolated from ginger, did not enhance TRAIL-induced apoptosis and down-regulate c-FLIP(L) expression. Taken together, our results demonstrated that 6-shogaol enhances TRAIL-mediated apoptosis in renal carcinoma Caki cells via ROS-mediated cytochrome c release and down-regulation of c-FLIP(L) expression.
Keywords:
6-Shogaol
TRAIL
ROS
c-FLIP(L)
Apoptosis
Department
Dept. of Immunology (면역학)
Dept. of Otorhinolaryngology (이비인후과학)
Publisher
School of Medicine
Citation
Chemico-Biological Interactions, Vol.228(null) : 69-78, 2015
Type
Article
ISSN
0009-2797
DOI
10.1016/j.cbi.2015.01.020
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35390
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