TY - JOUR
T1 - Direct inhibitory effect of curcumin on Src and focal adhesion kinase activity
AU - Leu, Tzeng Horng
AU - Su, Shu Li
AU - Chuang, Ya Chun
AU - Maa, Ming Chei
N1 - Funding Information:
We thank Dr. Sarah J. Parsons for providing the monoclonal Src antibody (GD11) and Suparat Charoenfuprasert for her assistance in preparation of this manuscript. These studies were supported by National Science Council grants to M.-C.M. (NSC 91-2311-B-040-002) and grants of NHRI (NHRI-EX-91-8932SL) and MOE Program for Promoting Academic Excellence of Universities (91-B-FA09-1-4) to T.-H.L.
PY - 2003/12/15
Y1 - 2003/12/15
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bcp.2003.08.017
DO - 10.1016/j.bcp.2003.08.017
M3 - Article
C2 - 14637190
AN - SCOPUS:0344962391
SN - 0006-2952
VL - 66
SP - 2323
EP - 2331
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 12
ER -