Emodin Regulates Apoptotic Pathway in Human Liver Cancer Cells

Abstract

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.

Targeted abrogation of diverse signal transduction cascades by emodin for the treatment of inflammatory disorders and cancer

“…Study on hepatocarcinoma cells Huh7, Hep3B, and HepG2 revealed that treatment of emodin retards NF-jB/p65 protein level, and Bcl-2 expression, with simultaneous increase in p53 levels. It releases mitochondrial cytochrome C and also activates caspase-8 and -9 [69].…”

A map describing the association between effective components of traditional Chinese medicine and signaling pathways in cancer cells in vitro and in vivo

“…Emodin induces apoptosis of the HeLa human cervical cell line by activation of the mitochondria apoptotic pathway (46). Cancer cell apoptosis also can be induced by emodin in the HepG2 human HCC cell line through activation of the p53 pathway and inhibition of the NF-κB/p65 pathway (47).…”

Inhibitory effect of emodin on migration, invasion and metastasis of human breast cancer MDA-MB-231 cells in vitro and in vivo

“…1A), an active monomer extracted from Rheum, Polygonum, Buckthorn and Senna, has been shown to be active against pancreatic (5,6), lung (7,8), breast (9,10), liver (11), prostate (12,13), ovarian (14), cervical (15), colon (16), gallbladder (17) and human tongue cancer SCC-4 cells (18,19). Moreover, it has been reported that emodin induces apoptosis of human breast cancer MCF-7 (20) and MDA-MB-453 cells (21).…”