Curcumin inhibits tyrosine kinase activity of p185(neu) and also depletes p185(neu1)
Journal
Clinical Cancer Research
Journal Volume
5
Journal Issue
7
Pages
1884-1891
Date Issued
1999
Author(s)
Abstract
Curcumin, a natural compound present in turmeric, possessing both anti- inflammatory and antioxidant effects, has been studied vigorously as a chemopreventative in several cancer models. The erbB2/neu gene-encoded p185(neu) tyrosine kinase is a potent oncoprotein. Overexpression of p185(neu) in breast cancer is known to be a poor prognostic factor. We investigated the effect of curcumin on p185(neu) tyrosine kinase and on the growth of breast cancer cell lines. Curcumin dose-dependently inhibited p185(neu) autophosphorylation and transphosphorylation in vitro and depleted p185(neu) protein in vivo. It dissociated the binding of p185(neu) with GRP94 (glucose-regulated protein), a molecular chaperone, and enhanced the depletion of p185(neu). The amount of p185(neu) protein on the cell membrane was drastically decreased after curcumin treatment. These data demonstrated a new mechanism of the anti-tyrosine kinase activity of curcumin. The growth of several breast cancer cell lines was inhibited; the IC50 ranged from 7 to 18 μM, which, however, did not correlate with the expression level of p185(neu). Colony formation in the soft agar assay, a hallmark of the transformation phenotype, was preferentially suppressed in p185(neu)- overexpressing cell lines by 5 μM curcumin (% of control, basal level versus overexpression: 59.3 versus 16.7%; P < 0.001 by Student's t test). Because curcumin effectively inhibited p185(neu) tyrosine kinase activity by depleting p185(neu) and potently suppressed the growth of multiple breast cancer cell lines, its therapeutic potential in advanced breast cancer is worthy of further investigation.
SDGs
Other Subjects
chaperone; curcumin; glucose regulated protein; oncoprotein; protein p185; protein tyrosine kinase; unclassified drug; advanced cancer; article; breast carcinoma; cancer cell culture; cancer growth; controlled study; Curcuma longa; enzyme activity; gene overexpression; human; human cell; oncogene c erb; oncogene neu; priority journal; protein phosphorylation; Antineoplastic Agents; Cell Adhesion; Cell Division; Colony-Forming Units Assay; Curcumin; Enzyme Inhibitors; Fluorescent Antibody Technique; HSP70 Heat-Shock Proteins; Humans; Kinetics; Membrane Proteins; Molecular Weight; Phosphorylation; Protein Binding; Protein-Tyrosine Kinases; Receptor, erbB-2; Subcellular Fractions; Tumor Cells, Cultured
Type
journal article