title: Glycyrrhetinic acid potently suppresses breast cancer invasion and metastasis by impairing the p38 MAPK-AP1 signaling axis.
abstract: BACKGROUND
  Radix Glycyrrhiza has been used in China for thousand years to treat cancer. However, focus on its tumor-suppressing mechanism has been concentrated on its effect on tumor cell growth and apoptosis.
  
  
  OBJECTIVE
  With the aid of a panel of human breast cancer cell lines, we reveal that glycyrrhetinic acid (GA), a major component of Radix Glycyrrhiza, is actually a significantly more potent agent to suppress invasion than cell survival.
  
  
  RESULTS
  GA effectively inhibits breast cancer cell MMP-2/MMP-9 expression; GA-induced reduction in the MMP-2/9 expression is apparently mediated by GA's ability to specifically inhibit the p38 MAPK activity and its downstream AP1 activation. Moreover, we show that GA down regulates the levels of Fra-1 and c-Jun, two main components of AP1 transcription complex in invasive breast cancer cells and that AP1-specific inhibitor abrogates breast cancer cell invasion. These results suggest that GA impairs the p38 MAPK-AP1 signaling axis, leading to the repression of breast cancer cell invasion. Finally, we demonstrate that GA effectively suppresses breast tumor outgrowth and pulmonary metastasis without causing animal weight loss or eliciting liver/kidney toxicity to the recipient animals.
  
  
  CONCLUSIONS
  This study indicates that GA represents a good candidate compound for the potential development of therapeutic drug.
authors.affiliation: Shanghai University of Traditional Chinese Medicine, Research Center for Traditional Chinese Medicine Complexity System , Shanghai 201203 , China +86 215 132 3013 ; shibingsu07@163.com.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Wang
authors.forename: Qian-Mei
authors.initials: QM
authors.lastname: Zhou
authors.forename: Yi-Yu
authors.initials: YY
authors.lastname: Lu
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Shuang
authors.initials: S
authors.lastname: Huang
authors.forename: Shi-Bing
authors.initials: SB
authors.lastname: Su
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000737:chemistry; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D018808:Transcription Factor AP-1; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D006034:Glycyrrhetinic Acid
keywords: MMP; breast cancer; glycyrrhetinic acid; invasion; p38 MAPK