SCOPE: 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.
METHODS AND 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.
CONCLUSION: 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.