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

• Published in: Carcinogenesis (New York) 1995-08, Vol.16 (8), p.1741-1745
• Main Authors: Korutla, Laxminarayana, Cheung, Joseph Y., Medelsohn, John, Kumar, Rakesh
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Biological and medical sciences; Calcium - metabolism; Cell Division - drug effects; Cell physiology; Curcumin - pharmacology; Epidermal Growth Factor - pharmacology; ErbB Receptors - metabolism; Fundamental and applied biological sciences. Psychology; Mice; Molecular and cellular biology; Phosphorylation; Responses to growth factors, tumor promotors, other factors
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/16.8.1741

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.