Antimetastatic potentials of flavones on oral cancer cell via an inhibition of matrix-degrading proteases

Objective: Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers with a poor prognosis due to frequent lymph node metastasis and local invasion. A growing number of in vitro studies have been conducted on the potential anticancer activity of flavonoids in various cancer cell lines. However, the antimetastatic activities of flavones, one subclass of flavonoids, in human oral squamous carcinoma SCC-4 cells have not been understood clearly. Design: The present study investigated the effect of four flavones on invasion and migration of SCC-4 cells to find that 7-hydroxyflavanone, 5,6,7-trihydroxyflavanone, and 4′,5,7-trihydroxyflavanone exerted a dose-dependent inhibitory effect on the invasion and migration of SCC-4 cells. Results: Results from zymography and Western blot showed that flavones treatment may decrease the expressions of matrix metalloproteinase (MMP)-2, urokinase plasminogen activator (u-PA) in a concentration-dependent manner, together with altered expression levels of their endogenous inhibitors, which are tissue inhibitor of metalloproteinase-2 (TIMP-2) and plasminogen activator inhibitor-1 (PAI-1). Furthermore, an in vivo chorioallantoic membrane (CAM) intravasation assay was also treated and analysed to reveal the antimetastatic effect. Conclusions: Our data suggest that 7-hydroxyflavanone, 5,6,7-trihydroxyflavanone, and 4′,5,7-trihydroxyflavanone could be applicable to be a potential antimetastatic agent of SCC-4 cells.