TY - JOUR T1 - Rhein Induced Apoptosis through the Endoplasmic Reticulum Stress, Caspase- and Mitochondria-dependent Pathways in SCC-4 Human Tongue Squamous Cancer Cells JF - In Vivo JO - In Vivo SP - 309 LP - 316 VL - 23 IS - 2 AU - WAN-WEN LAI AU - JAI-SING YANG AU - KUANG-CHI LAI AU - CHAO-LIN KUO AU - CHENG-KUANG HSU AU - CHIEN-KUO WANG AU - CHING-YAO CHANG AU - JEN-JYH LIN AU - NOU-YING TANG AU - PO-YUAN CHEN AU - WEN-WEN HUANG AU - JING-GUNG CHUNG Y1 - 2009/03/01 UR - http://iv.iiarjournals.org/content/23/2/309.abstract N2 - Rhein, an anthraquinone compound, can be found in the rhizome of rhubarb, a traditional Chinese medicine herb showing antitumor activity. In this study, it was observed that rhein induced S-phase arrest through the inhibition of p53, cyclin A and E and it induced apoptosis through the endoplasmic reticulum stress by the production of reactive oxygen species (ROS) and Ca2+ release, mitochondrial dysfunction, and caspase-8, -9 and -3 activation in human tongue cancer cell line (SCC-4). The most efficient induction of apoptosis was observed at 30 μM for 24 h. Mechanistic analysis demonstrated that rhein induced changes in the ratio of Bax/Bcl-2 based on the decrease of Bcl-2 levels, the loss of mitochondrial membrane potential, cytochrome c release from the mitochondria and the activation of caspase-9 and -3. The data demonstrated that rhein induces apoptosis in SCC-4 cells via caspase, ROS and mitochondrial death pathways. ER -