薑黃素(Curcumin)是一個歷史悠久廣為人知的天然食用色素，它具有抗發炎、抗氧化、以及抗癌的效果。在本文研究中，我們發現薑黃素可以抑制c-Src的蛋白質表現。為進一步探討其對Src kinase活性的影響，我們以v-Src癌化之細胞 (IV5)為研究材料，發現薑黃素處理後的IV5細胞，其Shc、Cortactin、FAK等多種Src受質的酪氨酸磷酸化減少。而在我們In vitro kinase的實驗裡，我們也証明了薑黃素可直接抑制Src的活性。由於Src活性的下降，使Shc的Pi-Tyr-317減少，進而降低ERK的活性，抑制v-Src癌化細胞的生長。此外，薑黃素也可直接及間接地抑制FAK的活性。藉由降低Cortactin的酪氨酸磷酸化及FAK酵素活性，薑黃素更減緩了v-Src癌化細胞的移動(Migration)。據我們的所知，這是第一篇有關薑黃素藉由抑制Src及FAK的酵素活性，進而抑制細胞生長及移動的報導。 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.
