Emodin was isolated from Rheum palmatum L. and exhibits an anticancer effect on 
human cancer cell lines, however, the molecular mechanisms of emodin-mediated 
apoptosis in human tongue cancer cells have not been fully investigated. In this 
study, treatment of human tongue cancer SCC-4 cells with various concentrations 
of emodin led to G2/M arrest through promoted p21 and Chk2 expression but 
inhibited cyclin B1 and cdc2; it also induced apoptosis through the pronounced 
release of cytochrome c from mitochondria and activations of caspase-9 and 
caspase-3. These events were accompanied by the generation of reactive oxygen 
species (ROS), disruption of mitochondrial membrane potential (delta psi(m)) and 
a decrease in the ratio of mitochondrial Bcl-2 and Bax content; emodin also 
promoted the levels of GADD153 and GRP78. The free radical scavenger 
N-acetylcysteine and caspase inhibitors markedly blocked emodin-induced 
apoptosis. Taken together, these findings suggest that emodin mediated oxidative 
injury (DNA damage) based on ROS production and ER stress based on the levels of 
GADD153 and GRP78 that acts as an early and upstream change in the cell death 
cascade to caspase- and mitochondria-dependent signaling pathways, triggers 
mitochondrial dysfunction from Bcl-2 and Bax modulation, mitochondrial 
cytochrome c release and caspase activation, consequently leading to apoptosis 
in SCC-4 cells.