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

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.

• Authors: Xiang Chen, Xiao-Ning Yuan, Zun Zhang, Peng-Ju Gong, Wei-Nan Yin, Qi Jiang, Jingjing Xu, Xiao-Long Xu, Yang Gao, Wen-Li Chen, Fang-Fang Chen, Yi-Hao Tian, Lei Wei, Jing-Wei Zhang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 889 Pg. 173493 (Dec 15 2020) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 32860808 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

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

Topics

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