Morin inhibits 12-O-tetradecanoylphorbol-13-acetate-induced hepatocellular transformation via activator protein 1 signaling pathway and cell cycle progression.
Flavonoids are constituents of fruits, vegetables, and plant-derived beverages, as well as components in herbal containing dietary supplements. They exhibit a remarkable spectrum of biochemical and pharmacological activities. In this study, we examined morin (3,5,7,2',4'-pentahydroxyflavone) for its effect on 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated human hepatocytes. Morin inhibited TPA-induced cellular transformation in Chang liver cells in a dose-dependent manner. Luciferase assay and electrophoretic mobility shift assay revealed that morin suppressed TPA-induced AP-1 activity, and the inhibition of AP-1 activity by morin was mediated through the inhibition of p38 kinase. Moreover, morin induced the S-phase arrest and inhibited the DNA synthesis in TPA-treated hepatocytes, suggesting that a cell cycle checkpoint was activated by morin to block DNA synthesis in S phase. In conclusion, our results suggested that morin was a potent anti-hepatocellular transformation agent that inhibited cellular transformation by suppressing the AP-1 activity and inducing the S-phase arrest in human hepatocytes.
Hsiang
Chien-Yun
CY
Graduate Institute of Medical Science, China Medical University, Taichung, Taiwan. cyhsiang@mail.cmu.edu.tw
Wu
Shih-Lu
SL
Ho
Tin-Yun
TY
D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047309:Flavones
D005419:Flavonoids; D013755:Tetradecanoylphorbol Acetate; D018808:Transcription Factor AP-1; C008548:morin; D047309:Flavones