Genistein and curcumin block TGF-β1-induced u-PA expression and migratory and invasive phenotype in mouse epidermal keratinocytes

Transforming growth factor-beta(1) (TGF-beta(1)) stimulates migration/invasion of mouse transformed keratinocytes and increases urokinase (u-PA) expression/secretion. In this report, we analyzed the biological behavior of two naturally occurring inhibitors of protein tyrosine kinases, genistein and curcumin, that could abrogate the enhancement of u-PA levels induced by TGF-beta(1) in transformed keratinocytes. Our results showed that genistein and curcumin blocked this response in a dose-dependent manner and also inhibited the TGF-beta(1)-induced synthesis of fibronectin, an early responsive gene to the growth factor. Both compounds also reduced TCF-beta(1)-stimulated cell migration and invasiveness. These results suggest that a tyrosine kinase-signaling pathway should be involved in TGF-beta(1)-mediated increased malignancy of transformed keratinocytes and that genistein and curcumin could play an important role in inhibiting tumor progression.