Direct inhibitory effect of curcumin on Src and focal adhesion kinase activity.
Curcumin (diferuloylmethane) is a well-known agent with anti-inflammatory, antioxidant, and anticarcinogenic properties. In this study, we observed that curcumin inhibited 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.
Leu
Tzeng-Horng
TH
Department of Pharmacology, College of Medicine, National Cheng Kung University, 70101 Tainan, Taiwan, ROC.
Su
Shu Li
SL
Chuang
Ya-Chun
YC
Maa
Ming-Chei
MC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005353:Fibronectins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D005353:Fibronectins; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases; D003474:Curcumin