title: The antimetastatic effects of resveratrol on hepatocellular carcinoma through the downregulation of a metastasis-associated protease by SP-1 modulation.
abstract: BACKGROUND
  The mortality and morbidity rates from cancer metastasis have not declined in Taiwan, especially because of hepatocellular carcinoma (HCC). Resveratrol has been shown to have benefits such as cardioprotection, providing antioxidative, anti-inflammatory, anti-cancer properties in previous studies. Therefore, HCC cells were subjected to treatment with resveratrol and then analyzed to determine the effects of resveratrol on the migration and invasion.
  
  
  RESULTS
  Modified Boyden chamber assays revealed that resveratrol treatment significantly inhibited cell migration and invasion capacities of Huh7 cell lines that have low cytotoxicity in vitro, even at a high concentration of 100 µM. The results of casein zymography and western blotting revealed that the activities and protein levels of the urokinase-type plasminogen activator (u-PA) were inhibited by resveratrol. Western blot analysis also showed that resveratrol inhibits phosphorylation of JNK1/2. Tests of the mRNA level, real-time PCR, and promoter assays evaluated the inhibitory effects of resveratrol on u-PA expression in HCC cells. The chromatin immunoprecipitation (ChIP) assay showed that reactive in transcription protein of nuclear factor SP-1 was inhibited by resveratrol.
  
  
  CONCLUSIONS
  Resveratrol inhibits u-PA expression and the metastasis of HCC cells and is a powerful chemopreventive agent. The inhibitory effects were associated with the downregulation of the transcription factors of SP-1 signaling pathways.
authors: School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors: Chao-Bin
authors: CB
authors: Yeh
authors: Ming-Ju
authors: MJ
authors: Hsieh
authors: Chiao-Wen
authors: CW
authors: Lin
authors: Hui-Ling
authors: HL
authors: Chiou
authors: Pen-Yuan
authors: PY
authors: Lin
authors: Tzy-Yen
authors: TY
authors: Chen
authors: Shun-Fa
authors: SF
authors: Yang
mesh_terms: D016588:Anticarcinogenic Agents / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D013267:Stilbenes / Q000008:administration & dosage*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D016329:Sp1 Transcription Factor; D013267:Stilbenes; D014568:Urokinase-Type Plasminogen Activator; D000077185:Resveratrol