title: Invadopodia-associated proteins blockade as a novel mechanism for 6-shogaol and pterostilbene to reduce breast cancer cell motility and invasion.
abstract: METHODS
  Invadopodia are actin-rich membrane protrusions of tumor cells that are thought to initiate the local migration and invasion during cancer metastasis. The blockade of invadopodia-associated proteins has been reported as a promising approach for prevention of tumor metastasis. The aim of this study was to investigate the modulatory effects of 6-shogaol and pterostilbene on invadopodia in aggressive breast cancer cells.
  
  
  RESULTS
  By wound-healing, transwell, and gelatin zymography assays, we found that 6-shogaol and pterostilbene effectively attenuated the motility and invasion of MDA-MB-231 cells, and suppressed the activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Further investigation into the underlying molecular mechanisms revealed that the levels of key modulators of invadopodium maturation, including c-Src kinase, cortactin, and membrane type 1-matrix metalloproteinase (MT1-MMP) decreased when cells were treated with 6-shogaol or pterostilbene.
  
  
  CONCLUSIONS
  These data suggest that the repression of these factors might affect the maturation of invadopodia, inhibiting the metastasis of MDA-MB-231 cells. In conclusion, the present study demonstrates for the first time that 6-shogaol and pterostilbene can inhibit invadopodium formation and MMP activity in highly invasive breast cancer cells. We suggest that these compounds may be clinically useful in chemopreventive treatments for metastatic breast cancer.
authors: Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan.
authors: Bo-Han
authors: BH
authors: Hong
authors: Chi-Hao
authors: CH
authors: Wu
authors: Chi-Tai
authors: CT
authors: Yeh
authors: Gow-Chin
authors: GC
authors: Yen
mesh_terms: D000199:Actins / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology; D000081247:CSK Tyrosine-Protein Kinase; D002396:Catechols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D051356:Cortactin / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D051879:Twist-Related Protein 1 / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000199:Actins; C495868:CTTN protein, human; D002396:Catechols; D051356:Cortactin; D009687:Nuclear Proteins; D012333:RNA, Messenger; D013267:Stilbenes; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C107773:pterostilbene; C040115:shogaol; D020796:Receptor, Platelet-Derived Growth Factor alpha; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14