계명대학교 의학도서관 Repository

Withaferin A sensitizes TRAIL-induced apoptosis through reactive oxygen species-mediated up-regulation of death receptor 5 and down-regulation of c-FLIP

Metadata Downloads
Author(s)
박종욱권택규
Alternative Author(s)
Park, Jong WookKwon, Taeg Kyu
Publication Year
2009
Abstract
Withaferin A (Wit A) has reportedly shown cytotoxicity in a variety of tumor cell lines. Here, we show
that cotreatment with subtoxic doses of Wit A and tumor necrosis factor-related apoptosis-inducing
ligand (TRAIL) induces apoptosis in human renal cancer cells, Caki cells, but not in human normal
mesangial cells. Moreover, the combined treatment with Wit A and TRAIL dramatically induces apoptosis
in various cancer cell types, suggesting that this combined treatment might offer an attractive strategy for
safely treating human cancers. Treatment of Caki cells with Wit A up-regulated death receptor 5 (DR5) in
a C/EBP homologous protein (CHOP)-dependent manner. Interestingly, a Wit A-induced increase in ROS
levels preceded the up-regulation of CHOP and DR5. The involvement of ROS in CHOP-mediated DR5 upregulation
was confirmed by the result that pretreatment with an antioxidant, NAC or catalase, inhibited
Wit A-induced up-regulation of both CHOP and DR5. We also found that Wit A treatment down-regulated
c-FLIP via NF-κB-mediated transcriptional control as well as ROS signaling pathways. Taken together, our
results show that DR5 up-regulation and c-FLIP down-regulation contribute to the sensitizing effect of
Wit A on TRAIL-mediated apoptosis in cancer cells.
Department
Dept. of Immunology (면역학)
Publisher
School of Medicine
Citation
Free Radical Biology and Medicine, Vol.46(12) : 1639-1649, 2009
Type
Article
ISSN
0891-5849
DOI
10.1016/j.freeradbiomed.2009.03.022
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35756
Authorize & License
  • AuthorizeOpen
  • EmbargoForever
Files in This Item:

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.