Cytotoxicity of dioscin in human gastric carcinoma cells through death receptor and mitochondrial pathways
Article first published online: 14 FEB 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 33, Issue 8, pages 712–722, August 2013
How to Cite
Hu, M., Xu, L., Yin, L., Qi, Y., Li, H., Xu, Y., Han, X., Peng, J. and Wan, X. (2013), Cytotoxicity of dioscin in human gastric carcinoma cells through death receptor and mitochondrial pathways. J. Appl. Toxicol., 33: 712–722. doi: 10.1002/jat.2715
- Issue published online: 21 JUN 2013
- Article first published online: 14 FEB 2012
- Manuscript Revised: 5 DEC 2011
- Manuscript Accepted: 5 DEC 2011
- Manuscript Received: 18 OCT 2011
- SGC-7901 cancer cells;
- death receptor pathway;
- mitochondrial pathway
In the present study, the antiproliferative effect of dioscin on human gastric carcinoma SGC-7901 cells was confirmed by 3-(4, 5-dimethylthiahiazo-zyl)-2, 5-dip-henytetrazolium bromide and flow cytometry assays. Through acridine orange–ethidium bromide double fluorescent staining, apoptotic morphology of the cells was observed. Radioimmunoassays showed that the tumor necrosis factor (TNF)-α concentration in cells treated with dioscin significantly increased compared with untreated cells. Several proteins and mRNA related to the mitochondrial and death receptor pathways were investigated. We found that the expression of Bid, bcl-2 and bcl-xl was markedly downregulated, and the expression of Bak and Bax was upregulated. In addition, cytochrome c was released from the mitochondria into the cytosol, which indicates activation of the mitrochondrial pathway by dioscin. Furthermore, upregulation of Fas, FasL (Fas ligand), TNF-α, TNF receptor-1, TNF receptor-associated factor 1 and Fas-associated protein with death domain demonstrated involvement of the death receptor pathway. Increased mRNA expression of p53 was also found in dioscin-treated SGC-7901 cells, and the activation of caspase-3 and −8 was also observed. Consequently, this study clarifies the mechanism underlying the anticancer effect of dioscin, and also indicates that dioscin may be a potential drug treatment for human gastric cancer. Copyright © 2012 John Wiley & Sons, Ltd.