The potentiation of curcumin on insulin-like growth factor-1 action in MCF-7 human breast carcinoma cells

Curcumin has anticarcinogenic and chernopreventive properties in a variety of experimental cancer models. Our in vitro studies have shown that curcurnin inhibits cell growth and induces apoptosis in MCF-7, a human breast carcinoma cell line. The insulin-like growth factor-1 (IGF-1) system, including IGFs (IGF-1 and IGF-2), IGF-IR (IGF-1 receptor) and IGFBPs (IGF binding proteins), has been implicated to play a critical role in the development of breast cancer. The aim of the present study was to investigate whether the growth inhibitory effects of curcurnin were related to changes of the IGF-1 system in MCF-7 cells. IGF-1 at 50 mu g/l in serum-free medium produced maximum proliferation and minimized apoptosis. However, curcumin exhibited a potent ability to blunt IGF-1-stimulated MCF-7 cell growth and reverse the IGF-1-induced apoptosis resistance. To determine whether curcurnin intervenes in IGF-I or IGFBP-3 secretion, MCF-7 cells were incubated in serum-free medium in the presence of various concentrations of curcurnin for indicated time periods. Curcumin decreased the secretion of IGF-1 with a concomitant increase of IGFBP-3 in a dose-dependent manner. Receptor tyrosine kinase assays revealed that IGF-1-stimulated IGF-IR tyrosine kinase activation was also abrogated by curcumin in a dose-dependent manner. Real-time fluorescence quantitative reverse transcriptase-polymerase chain reaction (RFQ-RT-PCR) further revealed that curcurnin suppressed IGF-IR gene expression at transcriptional level. In conclusion, the inhibition of cell growth and induction of apoptosis by curcurnin in MCF-7 cells might be mediated, at least partially, by its ability to down-regulate the IGF-I axis. (c) 2007 Elsevier Inc. All rights reserved.