INHIBITION OF LIGAND-INDUCED ACTIVATION OF EPIDERMAL GROWTH-FACTOR RECEPTOR TYROSINE PHOSPHORYLATION BY CURCUMIN

被引:108
作者
KORUTLA, L
CHEUNG, JY
MENDELSOHN, J
KUMAR, R
机构
[1] PENN STATE UNIV,COLL MED,DEPT MED,HERSHEY,PA 17033
[2] PENN STATE UNIV,COLL MED,DEPT CELLULAR & MOLEC PHYSIOL,HERSHEY,PA 17033
[3] MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021
关键词
D O I
10.1093/carcin/16.8.1741
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We explored the regulation of epidermal growth factor (EGF)-mediated activation of EGF receptor (EGF-R) phosphorylation by curcumin (diferuloyl-methane), a recently identified kinase inhibitor, in cultured NIH 3T3 cells expressing human EGF-R. Treatment of cells with a saturating concentration of EGF for 5-15 min induced increased EGF-R tyrosine phosphorylation by 4- to 11-fold and this was inhibited in a dose- and time-dependent manner by up to 90% by curcumin, which also inhibited the growth of EGF-stimulated cells, There was no effect of curcumin treatment on the amount of surface expression of labeled EGF-R and inhibition of EGF-mediated tyrosine phosphorylation of EGF-R by curcumin was mediated by a reversible mechanism. In addition, curcumin also inhibited EGF-induced, but not bradykinin-induced, calcium release. These findings demonstrate that curcumin is a potent inhibitor of a growth stimulatory pathway, the ligand-induced activation of EGF-R, and may potentially be useful in developing anti-proliferative strategies to control tumor cell growth.
引用
收藏
页码:1741 / 1745
页数:5
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