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

J Cell Biochem 2008 Jun;104(3):895-907

Department of Immunology and Chronic Disease Research Center and Institute for Medical Science, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712, South Korea.

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.

Download full-text PDF

Source
http://doi.wiley.com/10.1002/jcb.21672
Publisher Site
http://dx.doi.org/10.1002/jcb.21672DOI Listing
June 2008
1 Read

Publication Analysis

Top Keywords

breast cancer
12
sanguinarine-induced apoptosis
12
cell death
12
cancer cells
8
mda-231 cells
8
sanguinarine trail
8
generation ros
8
apoptosis
7
sanguinarine
6
bcl-2
5
sanguinarin-induced apoptosis
4
death sanguinarin-induced
4
involvement ros
4
suggesting involvement
4
ros cell
4
protein levels
4
ciap2 xiap
4
xiap c-flips
4
c-flips reduced
4
bcl-2 ciap2
4

References

(Supplied by CrossRef)

Adhami et al.
Clin Cancer Res 2003

Adhami et al.
Mol Cancer Ther 2004

Ahmad et al.
Clin Cancer Res 2000

Ahsan et al.
Cancer Lett 2007

Butler et al.
Int J Cancer 2006

Chau et al.
J Exp Med 2005

Clark et al.
Mol Cancer Ther 2002

Colombo et al.
Pharmacol Res 1996

Day et al.
Biochem Pharmacol 2006

Faddeeva et al.
Tsitologiia 1997

Firatli et al.
J Clin Periodontol 1994

Similar Publications