題名: Emodin Induces Apoptosis of Human Tongue Squqmous Cancer SCC-4 Cells through Reactive Oxygen Species and Mitochondria-dependent Pathways
作者: Shuw-Yuan Lin;Wan-Wen Lai;Chin-Chin ho;Fu-Shun Yu;Guang-Wei
Chen;Jai-Sing Yang;Kuo-Ching Liu;Meng-Liang Lin;Ping-Ping Wu;Ming-Jen Fan;Jing-Gung Chung
貢獻者: Department of Biotechnology
關鍵詞: ROS;ER stress;cell death;anthraquinone 日期: 2009
上傳時間: 2010-03-15T08:10:41Z 出版者: Asia University
摘要: 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 (ΔΨm) 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
