Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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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)
  • Published : 2012.04.30
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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.

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References

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