Curcumin (diferulonylmethane) is a well-known agent with anti-inflammatory, antioxidant, and anticarcinogenic properties. In this study, we observed that curcumin could downregulate the expression of c-Src in colon cancer cells. To further study its effect on the kinase activity of Src, C3H10T1/2 fibroblasts expressing v-Src (IV5) were utilized as our study material. Curcumin treatment could inhibit the kinase activity of v-Src, which led to a decrease in tyrosyl substrate phosphorylation of Shc, cortactin, and FAK. Our in vitro kinase experiment revealed that the inhibitory effect of curcumin on Src could be direct. Consistent with the abrogation of Src activity was the reduction of Src Tyr-416 phosphorylation, Src-mediated Shc Tyr-317 phosphorylation, decreased ERK activation, and cell proliferation in v-Src transformed cells. Remarkably, curcumin not only exerted its negative effect on FAK via the disappearance of Src-mediated FAK phosphorylation, but also directly inhibited its enzymatic activity. Concurrent to reduced cortactin tyrosyl phosphorylation and FAK kinase activity was the abolishment of v-Src-mediated cell mobility. To our knowledge, this is the first report indicating that curcumin can retard cellular growth and migration via downregulation of Src and FAK kinase activity.
