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

Abstract

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a natural occurring anthraquinone derivative isolated from roots and barks of numerous plants, molds, and lichens. It is found as an active ingredient in different Chinese herbs including Rheum palmatum and Polygonam multiflorum, and has diuretic, vasorelaxant, anti-bacterial, anti-viral, anti-ulcerogenic, anti-inflammatory, and anti-cancer effects. The anti-inflammatory effects of emodin have been exhibited in various in vitro as well as in vivo models of inflammation including pancreatitis, arthritis, asthma, atherosclerosis and glomerulonephritis. As an anti-cancer agent, emodin has been shown to suppress the growth of various tumor cell lines including hepatocellular carcinoma, pancreatic, breast, colorectal, leukemia, and lung cancers. Emodin is a pleiotropic molecule capable of interacting with several major molecular targets including NF-κB, casein kinase II, HER2/neu, HIF-1α, AKT/mTOR, STAT3, CXCR4, topoisomerase II, p53, p21, and androgen receptors which are involved in inflammation and cancer. This review summarizes reported anti-inflammatory and anti-cancer effects of emodin, and re-emphasizes its potential therapeutic role in the treatment of inflammatory diseases and cancer.

Keywords: 12-O-tetradecanoylphorbol-13-acetate; AKT; Angiogenesis; Apoptosis; CK2; COX; CXCR; Cancer; EGF; ELAM; ERK; Emodin; FAK; GRB-2; HDAC; HIF-1α; HMGB1; HSP; ICAM; IKK; IL; IκB; IκB kinase enzyme complex; JAK2; LRP1; MAPK; MMP; Metastasis; NF-κB; PI3K; PKC; PPAR-γ; ROS; STAT3; TGF; TLR4; TNF-related apoptosis-inducing ligand; TNF-α; TPA; TRAIL; TRB-3; VCAM-1; VEGF; X-linked inhibitor of apoptosis; XIAP; bFGF; basic-fibroblast growth factor; casein kinase II; cdk; chemokine (C-X-C motif) receptor; cyclin-dependent kinase; cyclooxygenase; endothelial cell leukocyte adhesion molecule; epidermal growth factor; extracellular regulated protein; extracellular signal-regulated kinases; focal adhesion kinase; growth factor receptor-bound protein 2; heat shock protein; high-mobility group protein B1; histone deacetylase; hypoxia inducible factor 1 alpha; iNOS; inducible nitric oxide synthase; inhibitory subunit of NF-κB; interleukin; intracellular adhesion molecule; janus kinase 2; lipoprotein receptor-related protein 1; matrix metalloproteinase; mitogen-activated protein kinase; nuclear factor-κB; peroxisome proliferator-activated receptor gamma; phosphatidylinositol 3-kinase; protein kinase C; reactive oxygen species; serine threonine protein kinase B; signal transducer and activator of transcription 3; toll-like receptor4; transforming growth factor; tribbles homolog 3; tumor necrosis factor; uPA; urokinase plasminogen activator; vascular cell adhesion molecule 1; vascular endothelial growth factor.