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Sanguinarine-Induced Apoptosis: Generation of ROS, Down-Regulation of Bcl-2, c-FLIP, and Synergy With TRAIL

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Author(s)
김신박종욱권택규
Alternative Author(s)
Kim, ShinPark, Jong WookKwon, Taeg Kyu
Publication Year
2008
Keyword
sanguinarineTRAILapoptosisreactive oxygen speciesBcl-2c-FLIP
Abstract
Sanguinarine is a benzophenanthridine alkaloid derived from the root of Sanguinaria canadensis and other poppy-fumaria species, possessing potent antibacterial, antifungal, and anti-inflammatory activities. In this study, we investigated the underling mechanisms by which sanguinarine induce apoptosis in human breast cancer MDA-231 cells. Treatment of MDA-231 cells with sanguinarine induced remarkable apoptosis accompanying the generation of ROS. Consistently, sanguinarine-induced apoptosis was mediated by the increased reproductive cell death. Pretreatment with NAC or GSH attenuated sanguinarine-induced apoptosis, suggesting the involvement of ROS in this cell death. During sanguinarin-induced apoptosis, protein levels of pro-caspase-3, Bcl-2, cIAP2, XIAP, and c-FLIPs were reduced. Sanguinarine-mediated apoptosis was substantially blocked by ectopic expression of Bcl-2 and cFLIPs. Additionally, we found that sub-lethal doses of sanguinarine remarkably sensitized breast cancer cells to TRAIL-mediated apoptosis, but the cell death induced by sanguinarine and TRAIL in combination was not blocked by overexpression of Bcl-2 or Akt. Therefore, combinatory treatment of sanguinarine and TRAIL may overcome the resistance of breast cancer cells due to overexpression of Akt or Bcl-2. J.
Department
Dept. of Immunology (면역학)
Institute for Medical Science (의과학연구소)
Publisher
School of Medicine
Citation
Journal of Cellular Biochemistry, Vol.104(3) : 895-907, 2008
Type
Article
ISSN
0730-2312
DOI
10.1002/jcb.21672
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/33973
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