Inhibition of Growth of Esophageal Cancer by Alantolactone via Wnt/β- Catenin Signaling

Anticancer Agents Med Chem. 2021;21(18):2525-2535. doi: 10.2174/1871520621666210112124546.

Abstract

Background: Alantolactone (AL) is a natural compound extracted from the roots of Inula Helenium L, which exerts an anti-tumor effect in a variety of cancer cell lines; however, its effect on esophageal cancer, a common malignancy with poor prognosis, remains unclear. Therefore, we aim to evaluate the effect of AL on esophageal cancer and to explore its underlying mechanism.

Objective: This study aims to determine whether AL has an anti-cancer effect on esophageal cancer cells and to explore its underlying mechanism.

Methods: The effect of AL on the proliferation and apoptosis of esophageal cancer cells was detected by MTT assay, colony formation assay, crystal violet assay, flow cytometry and hoechst apoptosis staining. The wound healing and Transwell invasion assay were performed to examine the effect of AL on the migration and invasion of esophageal cancer cells. Luciferase reporter system and Western blot were used to study the anti-tumor mechanism of AL on esophageal cancer cells. The subcutaneous murine xenograft model was employed to verify the effects of AL on esophageal cancer cells.

Results: MTT assay, colony formation assay and crystal violet assay found that AL inhibited the growth of esophageal cancer cells. Hoechst staining and flow cytometry analysis showed that AL induced apoptosis in esophageal cancer through mitochondrial pathway. Transwell assay and wound healing assays showed that AL inhibited the metastasis and invasion of esophageal cancer cells. Wnt/ β-catenin signaling may contribute to the mechanism of the inhibition. The anti-tumor effect of AL on esophageal cancer cells was validated on murine xenograft model.

Conclusion: Our data indicate that AL inhibits proliferation, migration, and invasion of esophageal cancer cells, and promote apoptosis of esophageal cancer cells through the Wnt/β-catenin signaling pathway.

Keywords: Alantolactone; Wnt signaling; anti-tumor; esophageal cancer; growth; β-Catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Female
  • Humans
  • Lactones / chemistry
  • Lactones / isolation & purification
  • Lactones / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Sesquiterpenes, Eudesmane / chemistry
  • Sesquiterpenes, Eudesmane / isolation & purification
  • Sesquiterpenes, Eudesmane / pharmacology*
  • Tumor Cells, Cultured
  • Wnt Signaling Pathway / drug effects
  • beta Catenin / antagonists & inhibitors
  • beta Catenin / metabolism

Substances

  • Antineoplastic Agents
  • Lactones
  • Sesquiterpenes, Eudesmane
  • beta Catenin
  • alantolactone