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.
Lai
Wan-Wen
WW
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.
Yang
Jai-Sing
JS
Lai
Kuang-Chi
KC
Kuo
Chao-Lin
CL
Hsu
Cheng-Kuang
CK
Wang
Chien-Kuo
CK
Chang
Ching-Yao
CY
Lin
Jen-Jyh
JJ
Tang
Nou-Ying
NY
Chen
Po-Yuan
PY
Huang
Wen-Wen
WW
Chung
Jing-Gung
JG
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