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Sanguinarine-induced apoptosis: generation of ROS, down-regulation of Bcl-2, c-FLIP, and synergy with TRAIL.

Kim, S; Lee, TJ; Leem, J; Choi, KS; Park, JW; Kwon, TK
Journal of cellular biochemistry, 104(3):895-907, 2008
Journal Title
Journal of cellular biochemistry
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.
MeSH terms
Anti-Infective Agents/pharmacologyApoptosis*Benzophenanthridines/pharmacology*CASP8 and FADD-Like Apoptosis Regulating Protein/metabolism*Cell Line, TumorDown-Regulation*Gene Expression Regulation, Neoplastic*Glutathione/metabolismHumansIsoquinolines/pharmacology*Models, BiologicalPlant Extracts/metabolismProto-Oncogene Proteins c-akt/metabolismProto-Oncogene Proteins c-bcl-2/metabolism*Reactive Oxygen Species*TNF-Related Apoptosis-Inducing Ligand/metabolism*
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Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
최, 경숙
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