Luteolin Inhibits Proliferation Induced by IGF-1 Pathway Dependent ERα in Human Breast Cancer MCF-7 Cells

The growth of many breast tumors is stimulated by IGF-1, which activates signal transduction pathways inducing cell proliferation. ER alpha is important in this process. The aim of the study was to investigate relationships in vitro among inhibitory effects of luteolin on the growth of MCF-7 cells, IGF-1 pathway and ER alpha. Our results showed that luteolin could effectively block IGF-1-stimulated MCF-7 cell proliferation in a dose- and time- dependent manner and block cell cycle progression and induce apoptosis evidenced by the flow cytometric detection of sub-G1DNA content. Luteolin markedly decreased IGF-1-depedent IGF-1R and Akt phosphorylation without affecting Erk1/2 phosphorylation. Further experiments pointed out that ER alpha was directly involved in IGF-1 induced cell growth inhibitory effects of luteolin, which significantly decreased ER alpha expression. Knockdown of ER alpha in MCF-7 cells by an ER alpha-specific siRNA decreased the IGF-1 induced cell growth inhibitory effects of luteolin. ER alpha is thus a possible target of luteolin. These findings indicate that the inhibitory effect of luteolin on the growth of MCF-7 cells is via inhibiting IGF-1 mediated PI3K-Akt pathway dependent of ER alpha expression.