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Endoplasmic reticulum stress mediates withaferin A-induced apoptosis in human renal carcinoma cells

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Author(s)
Min Jung ChoiEun Jung ParkKyoung Jin MinJong-Wook ParkTaeg Kyu Kwon
Keimyung Author(s)
Park, Jong WookKwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Toxicol In Vitro
Issued Date
2011
Volume
25
Issue
3
Keyword
Withaferin AEndoplasmic reticulum stressApoptosisCHOPUnfolded protein response
Abstract
The accumulation ofmisfolded proteins in the lumen of the endoplasmic reticulum(ER) results in cellular
stress that initiates a specialized response designated as the unfolded protein response. ER stress has
been implicated in a variety of common diseases, such as diabetes, ischemia and neurodegenerative dis-
orders. Withaferin A, a major chemical constituent of Withania somnifera, has been reported to inhibit
tumor cell growth. We show that withaferin A induced a dose-dependent apoptotic cell death in several
types of human cancer cells, as measured by FACS analysis and PARP cleavage. Treatment of Caki cells
with withaferin A induced a number of signature ER stress markers, including phosphorylation of eukary-
otic initiation factor-2a (eIF-2 a), ER stress-specific XBP1 splicing, and up-regulation of glucose-regulated
protein (GRP)-78. In addition, withaferin A caused up-regulation of CAAT/enhancer-binding protein-
homologous protein (CHOP), suggesting the induction of ER stress. Pretreatment with N-acetyl cysteine
(NAC) significantly inhibited withaferin A-mediated ER stress proteins and cell death, suggesting that
reactive oxygen species (ROS) mediate withaferin A-induced ER stress. Furthermore, CHOP siRNA or inhi-
bition of caspase-4 activity attenuated withaferin A-induced apoptosis. Taken together, the present study
provides strong evidence supporting an important role of the ER stress response in mediating withaferin
A-induced apoptosis. Keywords:
Withaferin A
Endoplasmic reticulum stress
Apoptosis
CHOP
Unfolded protein response
Keimyung Author(s)(Kor)
박종욱
권택규
Publisher
School of Medicine
Citation
Min Jung Choi et al. (2011). Endoplasmic reticulum stress mediates withaferin A-induced apoptosis in human renal carcinoma cells. Toxicol In Vitro, 25(3), 692–698. doi: 10.1016/j.tiv.2011.01.010
Type
Article
ISSN
0887-2333
Source
http://lps3.www.sciencedirect.com.proxy.dsmc.or.kr/science/article/pii/S0887233311000233?via%3Dihub
DOI
10.1016/j.tiv.2011.01.010
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34656
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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