title: Inhibitory effects of isoliquiritigenin on the migration and invasion of human breast cancer cells.
abstract: BACKGROUND
  Isoliquiritigenin (ISL) is a natural phenolic compound extracted from licorice. Previous studies have shown that ISL is a potent antioxidant with anti-inflammatory and antitumor activities. The anti-invasive activity of ISL was still unclear. The actual causes of death for most breast cancer patients were due to the tumor metastasis. Attenuating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) is well known to prevent tumor metastasis.
  
  
  OBJECTIVE
  The purpose of this study is to investigate the effects of ISL on VEGF and MMP expression in highly metastatic human breast cancer cell line, MDA-MB-231.
  
  
  RESULTS
  ISL reduced the secretions and protein levels of VEGF. The VEGF upstream regulatory protein, hypoxia-inducible factor 1-alpha (HIF-1α), was also reduced after ISL treatment. Moreover, ISL inhibited the expression and gelatinolytic activity of MMP-2 and MMP-9 which were confirmed by western blot and gelatin zymography assay. Additionally, the anti-migratory activity of ISL was further confirmed by chamber migration assay and wound migration assay. Upstream signaling pathways, including the expression of phosphatidylinositol-3 kinase (PI3K), the phosphorylation of p38 and Akt kinase and NF-κB DNA binding activity, were suppressed by ISL.
  
  
  CONCLUSIONS
  These findings suggest that ISL suppresses the migration of MDA-MB-231 cells by inhibiting the upstream signaling pathways.
authors: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan, Republic of China.
authors: Kai-Lee
authors: KL
authors: Wang
authors: Shih-Min
authors: SM
authors: Hsia
authors: Chia-Jung
authors: CJ
authors: Chan
authors: Full-Young
authors: FY
authors: Chang
authors: Chih-Yang
authors: CY
authors: Huang
authors: Da-Tian
authors: DT
authors: Bau
authors: Paulus S
authors: PS
authors: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D047188:Chalcones / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism; D042361:Mammary Glands, Human / Q000187:drug effects* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047188:Chalcones; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D061965:Matrix Metalloproteinase Inhibitors; D009363:Neoplasm Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C040920:isoliquiritigenin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9