Emodin Regulates Apoptotic Pathway in Human Liver Cancer Cells
Article first published online: 7 MAY 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Volume 27, Issue 2, pages 251–257, February 2013
How to Cite
Yu, J.-Q., Bao, W. and Lei, J.-C. (2013), Emodin Regulates Apoptotic Pathway in Human Liver Cancer Cells. Phytother. Res., 27: 251–257. doi: 10.1002/ptr.4703
- Issue published online: 4 FEB 2013
- Article first published online: 7 MAY 2012
- Manuscript Accepted: 26 MAR 2012
- Manuscript Revised: 17 MAR 2012
- Manuscript Received: 27 DEC 2011
- National Natural Science Foundation of China. Grant Numbers: 30970294, 31070317
- signaling pathway
Emodin, a natural anthraquinone, has been reported to possess antiproliferative effects in many cancer cell lines. However, anticancer mechanism against human liver cancer remains unclear. In this study, we observed that emodin induced apoptosis in HepG2 cells and caused a significant accumulation of cells in the G1 phase. Western blot data showed that emodin treatment caused the increasing of release of cytochrome c into cytosol from mitochondria and the activation of caspase-8 and caspase-9, which suggest that the intrinsic and extrinsic pathways could be involved. Emodin treatment also resulted in a dose-dependent accumulation of intracellular reactive oxygen species. Furthermore, emodin increased the protein level of p53 and decreased the protein level of NF-κB/p65 in HepG2 cells, which indicated these two regulators might play a role in emodin-induced apoptosis. Computational modeling showed that emodin could directly bind to the BH3 domain of Bcl-2 through forming one hydrogen bond with Ala146 residue in Bcl-2. From these examinations, emodin not only significantly downregulated expression of Bcl-2 but also inhibited the heterodimerization of Bcl-2 with Bax because of strong interaction between emodin and Bcl-2. These suggest that emodin induces apoptosis in liver cancer cell line through a multifaceted complex cascade of events. Copyright © 2012 John Wiley & Sons, Ltd.