Introduction
Aloe-emodin is a natural active compound present in the leaves of Aloe vera (Reynolds, 1985). Some studies have indicated that aloe-emodin has a number of biological properties, including antiviral, antimicrobial, and hepatoprotective activities (Eshun and He, 2004). Aloe-emodin has also been reported to exhibit an anticancer activity on neuroectodermal tumors, lung squamous cell carcinoma, and hepatoma cells (Pecere et al., 2000, Lee et al., 2001, Kuo et al., 2002). In addition, aloe-emodin has been shown to inhibit S-phase progression in a transformed glia cell line and in a human glioma cell line, sensitize HeLa cells to As2O3 via the generation of reactive oxygen species, and affect the anticancer activity of cisplatin through blocking the activation of extracellular signal-regulated kinase (Acevedo-Duncan et al., 2004, Yi et al., 2004, Mijatovic et al., 2005). However, the effect of aloe-emodin on human gastric cancer cells has not yet been studied.
Apoptosis is an actively regulated process of cell death and the intrinsic pathway of apoptosis involves mitochondria (Penninger and Kroemer, 2003). Mitochondrial outer membrane permeabilization in response to cell death triggers (e.g., DNA damage) is an important early step which is regulated by Bcl-2 and controls the release of proteins, such as cytochrome c, from the mitochondria to the cytoplasm where they initiate apoptosis, ultimately leading to cell death (Kim et al., 2006). Apoptosis-inducing factor, another mitochondrial protein that is released into the cytosol and nucleus, induces chromatin condensation and DNA fragmentation (Susin et al., 1999). Most likely, members of caspase superfamily will be produced and activated that will hasten the cell death process involving the caspase-dependent apoptotic pathway (Kim et al., 2006).
Casein kinase II is a conserved and ubiquitous protein serine/threonine kinase engaged in various functions, including normal and abnormal cell proliferation (Kikkawa et al., 1992). Remarkable, casein kinase II is localized in both the cytoplasm and the nuclear compartment of healthy cells, but is predominantly present in the nuclear compartment of cancer cells and basically deregulated in all carcinoma studied to date (Ahmad et al., 2005). Recent evidence links casein kinase II to apoptosis (Ahmed et al., 2002). A role of casein kinase II in the modulation of caspase susceptibility has been observed with Bid, a proapoptotic member of the Bcl-2 family. It was shown that casein kinase II could phosphorylate Bid, close to the caspase-8 cleavage site, thereby preventing cells from undergoing apoptosis (Desagher et al., 2001). Thus, casein kinase II is an important target for the treatment of cancer as disruption of the casein kinase II activity prevents the phosphorylation of Bid thereby allowing the cleavage of Bid by caspases followed by apoptosis (Ahmad et al., 2005, Unger et al., 2004). Interestingly, an extensive downregulation of casein kinase II by antisense casein kinase II in prostate cancer xenografts eventually led to a complete disappearance of the tumor (Ahmad et al., 2005).