Inhibition of ligand-induced activation of epidermal growth factor receptor tyrosine phosphorylation by curcumin

作者：Laxminarayana Korutla, Joseph Y. Cheung, John Medelsohn, Rakesh Kumar · 发表于：Carcinogenesis · 年份：1995 · DOI：10.1093/carcin/16.8.1741 · 被引用次数：133 · 研究领域：HER2/EGFR in Cancer Research、Retinoids in leukemia and cellular processes、Glycosylation and Glycoproteins Research

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.