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http://dx.doi.org/10.7314/APJCP.2012.13.4.1431

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

Wang, Li-Meng (Liaoning Provincial Key Laboratory of Biotechnology and Drug Discover, College of Life Science, Liaoning Normal University)
Xie, Kun-Peng (Liaoning Provincial Key Laboratory of Biotechnology and Drug Discover, College of Life Science, Liaoning Normal University)
Huo, Hong-Nan (Liaoning Provincial Key Laboratory of Biotechnology and Drug Discover, College of Life Science, Liaoning Normal University)
Shang, Fei (Liaoning Provincial Key Laboratory of Biotechnology and Drug Discover, College of Life Science, Liaoning Normal University)
Zou, Wei (Liaoning Provincial Key Laboratory of Biotechnology and Drug Discover, College of Life Science, Liaoning Normal University)
Xie, Ming-Jie (Liaoning Provincial Key Laboratory of Biotechnology and Drug Discover, College of Life Science, Liaoning Normal University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.4, 2012 , pp. 1431-1437 More about this Journal
Abstract
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-l-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-l-dependent IGF-IR and Akt phosphorylation without affecting Erk1/2 phosphorylation. Further experiments pointed out that $ER{\alpha}$ was directly involved in IGF-l 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-l 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-l mediated PI3K-Akt pathway dependent of $ER{\alpha}$ expression.
Keywords
Breast cancer; IGF-1; $ER{\alpha}$; luteolin; MCF-7;
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