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

Abstract

The growth of many breast tumors is stimulated by IGF-1, which activates signal transduction pathways inducing cell proliferation. ER α 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 α. 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-dependent IGF-1R and Akt phosphorylation without affecting Erk1/2 phosphorylation. Further experiments pointed out that ER α was directly involved in IGF-1 induced cell growth inhibitory effects of luteolin, which significantly decreased ER α expression. Knockdown of ER α in MCF-7 cells by an ER α -specific siRNA decreased the IGF-1 induced cell growth inhibitory effects of luteolin. ER α is thus a possible target of luteolin. These findings indicate that the inhibitory effect of luteolinon the growth of MCF-7 cells is via inhibiting IGF-1 mediated PI3K-Akt pathway dependent of ER α expression.