Rhein inhibits TPA-induced activator protein-1 activation and cell transformation by blocking the JNK-dependent pathway.
Rhein (4,5-Dihydroxyanthraquinone-2-carboxylic acid), a constituent enriched in the rhizome of rhubarb (R. palmatum L. or R. tanguticum Maxim), is a traditional Chinese herb used as a laxative and stomachic drug. In the present study, we investigated the anti-carcinogenesis of rhein by using mouse epidermal cell JB6 line, an in vitro model for elucidating the molecular mechanisms of cancer chemopreventive agents. Rhein is shown to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation and activator protein-1 (AP-1) activation in a dose-dependent manner. Signal cascade analysis revealed that rhein inhibits the phosphorylation and abundance of c-Jun protein, c-Jun NH2-terminal kinase (JNK) phosphorylation, but does not inhibit the phosphorylation of extracellular signal-regulated protein kinase (ERK) and p38 kinase. Thus, these results provide the first evidence suggesting that rhein inhibits AP-1 activity and cell transformation through the inhibition of a JNK-dependent, ERK- and p38-independent molecular mechanism.
Lin
Shigang
S
Department of Biochemical Science and Technology, Department of Agricultural Science, Faculty of Agriculture, Kagoshima University, Kagoshima 890-0065, Japan.
Li
Jian-Jian
JJ
Fujii
Makoto
M
Hou
De-Xing
DX
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D008156:Luciferases / Q000378:metabolism; D048670:MAP Kinase Kinase 4; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008956:Models, Chemical; D010766:Phosphorylation; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D048051:p38 Mitogen-Activated Protein Kinases
D000880:Anthraquinones; D004791:Enzyme Inhibitors; D018808:Transcription Factor AP-1; D008156:Luciferases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D013755:Tetradecanoylphorbol Acetate; C020491:rhein