Wnt/β-catenin pathway mediates (-)-Epigallocatechin-3-gallate (EGCG) inhibition of lung cancer stem cells

Biochem Biophys Res Commun. 2017 Jan 1;482(1):15-21. doi: 10.1016/j.bbrc.2016.11.038. Epub 2016 Nov 9.

Abstract

Cancer stem cells (CSCs) play essential role in the progression of many tumors. Wnt/β-catenin pathway is crucial in maintaining the stemness of CSCs. (-)-Epigallocatechin-3-gallate (EGCG), the major bioactive component in green tea, has been shown to possess anti-cancer activity. To date, the interventional effect of EGCG on lung CSCs has not been elucidated yet. In the present study, tumorsphere formation assay was used to enrich lung CSCs from A549 and H1299 cells. We revealed that Wnt/β-catenin pathway was activated in lung CSCs, and downregulation of β-catenin, abolished lung CSCs traits. Our study further illustrated that EGCG effectively diminished lung CSCs activity by inhibiting tumorsphere formation, decreasing lung CSCs markers, suppressing proliferation and inducing apoptosis. Moreover, We showed that EGCG downregulated Wnt/β-catenin activation, while upregulation of Wnt/β-catenin dampened the inhibitory effects of EGCG on lung CSCs. Taken together, these results demonstrated the role of Wnt/β-catenin pathway in regulating lung CSCs traits and EGCG intervention of lung CSCs. Findings from this study could provide new insights into the molecular mechanisms of lung CSCs intervention.

Keywords: EGCG; Inhibition; Lung cancer stem cells; Wnt/β-catenin pathway.

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Wnt Signaling Pathway / drug effects*

Substances

  • Antineoplastic Agents
  • Catechin
  • epigallocatechin gallate