Betulinic acid inhibits cell proliferation and migration in gastric cancer by targeting the NF-κB/VASP pathway

Eur J Pharmacol. 2020 Dec 15:889:173493. doi: 10.1016/j.ejphar.2020.173493. Epub 2020 Aug 26.

Abstract

Gastric cancer (GC) is one of the most common malignant neoplasms of the digestive system, with China leading in terms of morbidity and mortality rates. Betulinic acid (BA) is a widely-occurring pentacyclic triterpenoid that has been reported to exhibit potent anti-inflammatory, antioxidant, and antitumor activities. BA can combat tumors by inducing apoptosis, regulating cell cycle, and inhibiting autophagy, but its mechanism of action in the context of GC is unclear. A preliminary study found that higher expression of vasodilator-stimulated phosphoprotein (VASP) was correlated with migration in the GC cell line. In this study, BGC-823 cells and MNK45 cells were treated with BA for investigating its effect on the proliferation and migration of cells. Moreover, the expression of VASP and upstream signal molecules were also investigated in this background. The results showed BA could inhibit the proliferation and migration the GC cells. Furthermore, NF-κB acted as a transcription factor to upregulate VASP expression. Moreover, BA could downregulate the expression of VASP at the protein and mRNA level by inhibiting NF-κB activity. In conclusion, these results suggest that BA could inhibit the expression of VASP by negatively regulating NF-κB, thereby inhibiting the proliferation and migration of the GC cells. Our study provides a theoretical basis for exploring the molecular mechanism underlying BA-induced inhibition of proliferation and migration in GC cells.

Keywords: Betulinic acid; Cell proliferation and migration; Gastric cancer; NF-κB; VASP.

MeSH terms

  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Betulinic Acid
  • Cell Adhesion Molecules / antagonists & inhibitors
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Movement / physiology
  • Cell Proliferation / drug effects*
  • Cell Proliferation / physiology
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems / methods
  • HEK293 Cells
  • Humans
  • Microfilament Proteins / antagonists & inhibitors
  • Microfilament Proteins / metabolism*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Pentacyclic Triterpenes / administration & dosage*
  • Phosphoproteins / antagonists & inhibitors
  • Phosphoproteins / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • Cell Adhesion Molecules
  • Microfilament Proteins
  • NF-kappa B
  • Pentacyclic Triterpenes
  • Phosphoproteins
  • vasodilator-stimulated phosphoprotein
  • Betulinic Acid