Metastasis is a major cause of mortality in cancer patients. Invadopodia are 
considered to be crucial structures that allow cancer cells to penetrate across 
the extracellular matrix (ECM) by using matrix metalloproteinases (MMPs). 
Previously, we isolated a highly invasive A431-III subline from parental A431 
cells by Boyden chamber assay. The A431-III cells possess higher invasive and 
migratory abilities, elevated levels of MMP-9 and an enhanced 
epithelial-mesenchymal transition (EMT) phenotype. In this study, we discovered 
that A431-III cells had an increased potential to form invadopodia and an 
improved capacity to degrade ECM compared with the original A431 cells. We also 
observed enhanced phosphorylation levels of cortactin and Src in A431-III cells; 
these phosphorylated proteins have been reported to be the main regulators of 
invadopodia formation. Flavonoids, almost ubiquitously distributed in food 
plants and plant food products, have been documented to exhibit anti-tumor 
properties. Therefore, it was of much interest to explore the effects of 
flavonoid antioxidants on the metastatic activity of A431-III cells. Exposure of 
A431-III cells to two potent dietary flavonoids, namely luteolin (Lu) and 
quercetin (Qu), caused inhibition of invadopodia formation and decrement in ECM 
degradation. We conclude that Lu and Qu attenuate the phosphorylation of 
cortactin and Src in A431-III cells. As a consequence, there ensues a disruption 
of invadopodia generation and the suppression of MMP secretion. These changes, 
in concert, bring about a reduction in metastasis.