Quercetin restrains TGF-β1-induced epithelial-mesenchymal transition by inhibiting Twist1 and regulating E-cadherin expression

Biochem Biophys Res Commun. 2018 Mar 25;498(1):132-138. doi: 10.1016/j.bbrc.2018.02.044. Epub 2018 Feb 7.

Abstract

Emerging evidence has indicated that transforming growth factor-beta 1 (TGF-β1) induces the epithelial-mesenchymal transition (EMT) in cancer cells, thus promoting their motility and invasiveness. Quercetin, a member of the polyphenolic flavonoid family, has been reported to display anticancer activity against a broad range of cancer cell types. Indeed, numerous studies have shown the cancer preventive effects and molecular mechanisms of quercetin in vitro using diverse cell model systems. However, the potential effect of quercetin on EMT remains unclear. In this study, we identified a unique function of quercetin in inhibiting the EMT process induced by TGF-β1. In particular, quercetin rescued the morphological changes and EMT-like phenotypes in TGF-β1-activated SW480 cells, and this inhibition of TGF-β1-induced EMT was mediated via the suppression of Twist1 expression. In addition, quercetin strongly suppressed TGF-β1-induced invasion of SW480 cells. Thus, quercetin may be considered a novel therapeutic agent for the treatment of patients with refractory cancer and for the prevention of the metastatic cascade initiated by EMT.

Keywords: Colorectal cancer (CRC); E-cadherin; Epithelial–mesenchymal transition (EMT); Quercetin (Que); Transforming growth factor-β1 (TGF-β1); Twist1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Neoplasm Metastasis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Promoter Regions, Genetic / genetics
  • Quercetin / pharmacology*
  • Transforming Growth Factor beta1 / adverse effects*
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism*

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • Nuclear Proteins
  • TWIST1 protein, human
  • Transforming Growth Factor beta1
  • Twist-Related Protein 1
  • Quercetin