title: Inhibition of ligand-induced activation of epidermal growth factor receptor tyrosine phosphorylation by curcumin.
abstract: 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.
authors.affiliation: Department of Medicine, Pennsylvania State University College of Medicine, Hershey 17033, USA.
authors.forename: L
authors.initials: L
authors.lastname: Korutla
authors.forename: J Y
authors.initials: JY
authors.lastname: Cheung
authors.forename: J
authors.initials: J
authors.lastname: Mendelsohn
authors.forename: R
authors.initials: R
authors.lastname: Kumar
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D003474:Curcumin; D002118:Calcium