Luteolin attenuates TGF-β1-induced epithelial-mesenchymal transition of lung cancer cells by interfering in the PI3K/Akt-NF-κB-Snail pathway

Life Sci. 2013 Dec 5;93(24):924-33. doi: 10.1016/j.lfs.2013.10.004. Epub 2013 Oct 17.

Abstract

Aims: Luteolin is a natural flavonoid that possesses a variety of pharmacological activities, such as anti-inflammatory and anti-cancer abilities. Whether luteolin regulates the transformation ability of lung cancer cells remains unclear. The current study aims to uncover the effects and underlying mechanisms of luteolin in regulation of and epithelial-mesenchymal transition of lung cancer cells.

Main methods: The lung adenocarcinoma A549 cells were used in this experiment; the cells were pretreated with luteolin followed by administration with TGF-β1. The expression levels of various cadherin and related upstream regulatory modules were examined.

Key findings: Pretreatment of luteolin prevented the morphological change and downregulation of E-cadherin of A549 cells induced by TGF-β1. In addition, the activation of PI3K-Akt-IκBa-NF-κB-Snail pathway which leads to the decline of E-cadherin induced by TGF-β1 was also attenuated under the pretreatment of luteolin.

Significance: We provide the mechanisms about how luteolin attenuated the epithelial-mesenchymal transition of A549 lung cancer cells induced by TGF-β1. This finding will strengthen the anti-cancer effects of flavonoid compounds via the regulation of migration/invasion and EMT ability of various cancer cells.

Keywords: EMT; Luteolin; NF-κB; PI3K/Akt; TGF-β1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / physiology*
  • Electrophoretic Mobility Shift Assay
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / genetics
  • Expectorants / pharmacology*
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Indicators and Reagents
  • Lung Neoplasms / pathology*
  • Luteolin / pharmacology*
  • NF-kappa B / physiology*
  • Oncogene Protein v-akt / physiology*
  • Phosphatidylinositol 3-Kinases / physiology*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Snail Family Transcription Factors
  • Transcription Factors / physiology*
  • Transforming Growth Factor beta1 / antagonists & inhibitors*
  • Transforming Growth Factor beta1 / pharmacology*

Substances

  • DNA-Binding Proteins
  • Expectorants
  • Indicators and Reagents
  • NF-kappa B
  • SNAI3 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors
  • Transforming Growth Factor beta1
  • Phosphatidylinositol 3-Kinases
  • Oncogene Protein v-akt
  • Luteolin