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

We explored the regulation of epidermal growth factor (EGF)-mediated a ctivation of EGF receptor (EGF-R) phosphorylation by curcumin (diferul oyl-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 ph osphorylation by 4- to 11-fold and this was inhibited in a dose- and t ime-dependent manner by up to 90% by curcumin, which also inhibited th e growth of EGF-stimulated cells, There was no effect of curcumin trea tment on the amount of surface expression of labeled EGF-R and inhibit ion of EGF-mediated tyrosine phosphorylation of EGF-R by curcumin was mediated by a reversible mechanism. In addition, curcumin also inhibit ed EGF-induced, but not bradykinin-induced, calcium release. These fin dings demonstrate that curcumin is a potent inhibitor of a growth stim ulatory pathway, the ligand-induced activation of EGF-R, and may poten tially be useful in developing anti-proliferative strategies to contro l tumor cell growth.