Rhein induced apoptosis through the endoplasmic reticulum stress, caspase- and mitochondria-dependent pathways in SCC-4 human tongue squamous cancer cells.
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 microM 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.
Department of Biological Science and Technology, School of Chinese Medicine, China Medical University, and Department of Medicine, China Medical University Hospital, No 91, Hsueh-Shih Road, Taichung 40402, Taiwan, ROC.
Wan-Wen
WW
Lai
Jai-Sing
JS
Yang
Kuang-Chi
KC
Lai
Chao-Lin
CL
Kuo
Cheng-Kuang
CK
Hsu
Chien-Kuo
CK
Wang
Ching-Yao
CY
Chang
Jen-Jyh
JJ
Lin
Nou-Ying
NY
Tang
Po-Yuan
PY
Chen
Wen-Wen
WW
Huang
Jing-Gung
JG
Chung
D000880:Anthraquinones / Q000494:pharmacology*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D017382:Reactive Oxygen Species; D013997:Time Factors; D014062:Tongue Neoplasms / Q000188:drug therapy*
D000880:Anthraquinones; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D020169:Caspases; C020491:rhein