title: Emodin induces apoptosis of human tongue squamous cancer SCC-4 cells through reactive oxygen species and mitochondria-dependent pathways.
abstract: 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.
authors.affiliation: Department of Food and Nutrition, Hung-Kuang University, Taichung, Taiwan.
authors.forename: Shuw-Yuan
authors.initials: SY
authors.lastname: Lin
authors.forename: Wan-Wen
authors.initials: WW
authors.lastname: Lai
authors.forename: Chin-Chin
authors.initials: CC
authors.lastname: Ho
authors.forename: Fu-Shun
authors.initials: FS
authors.lastname: Yu
authors.forename: Guang-Wei
authors.initials: GW
authors.lastname: Chen
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Liu
authors.forename: Meng-Liang
authors.initials: ML
authors.lastname: Lin
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Wu
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Fan
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung