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
相关论文
共 28 条
[21]   CURCUMIN IS A NONCOMPETITIVE AND SELECTIVE INHIBITOR OF PHOSPHORYLASE-KINASE [J].
REDDY, S ;
AGGARWAL, BB .
FEBS LETTERS, 1994, 341 (01) :19-22
[22]  
REISS M, 1992, CANCER RES, V51, P6254
[23]   LIGAND ACTIVATION OF OVEREXPRESSED EPIDERMAL GROWTH-FACTOR RECEPTORS TRANSFORMS NIH 3T3 MOUSE FIBROBLASTS [J].
RIEDEL, H ;
MASSOGLIA, S ;
SCHLESSINGER, J ;
ULLRICH, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (05) :1477-1481
[24]   PHARMACOLOGY OF DIFERULOYL METHANE (CURCUMIN), A NONSTEROIDAL ANTIINFLAMMATORY AGENT [J].
SRIMAL, RC ;
DHAWAN, BN .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 1973, 25 (06) :447-452
[25]   SIGNAL TRANSDUCTION BY RECEPTORS WITH TYROSINE KINASE-ACTIVITY [J].
ULLRICH, A ;
SCHLESSINGER, J .
CELL, 1990, 61 (02) :203-212
[26]  
VANDEVIJVER MJ, 1991, J BIOL CHEM, V266, P7503
[27]   BLOCKING OF EGF-DEPENDENT CELL-PROLIFERATION BY EGF RECEPTOR KINASE INHIBITORS [J].
YAISH, P ;
GAZIT, A ;
GILON, C ;
LEVITZKI, A .
SCIENCE, 1988, 242 (4880) :933-935
[28]   GROWTH-FACTOR RECEPTOR TYROSINE KINASES [J].
YARDEN, Y ;
ULLRICH, A .
ANNUAL REVIEW OF BIOCHEMISTRY, 1988, 57 :443-478