Betulonic Acid, as One of the Active Components of the Celastrus orbiculatus Extract, Inhibits the Invasion and Metastasis of Gastric Cancer Cells by Mediating Cytoskeleton Rearrangement In Vitro

Molecules. 2022 Feb 2;27(3):1025. doi: 10.3390/molecules27031025.

Abstract

Gastric cancer is a type of malignant tumor that seriously threatens human life and health. Invasion and metastasis present difficulties in the treatment of gastric cancer, and the remodeling of the tumor cytoskeleton plays an important role in mediating the ability of tumor cells to achieve invasion and metastasis. Previous experimental results suggest that Celastrus orbiculatus extract can regulate cytoskeletal remodeling in gastric cancer, but the active component has not been determined. Betulonic acid, as an effective component of COE, inhibits the invasion and metastasis of gastric cancer cells by regulating cytoskeletal remodeling in vitro; its specific mechanisms have been studied here. After betulonic acid was dissolved, it was diluted to various working concentrations in RPMI-1640 medium and added to AGS, HGC-27 and GES-1 cell lines. Cell viability was assessed by CCK-8 and colony formation assays. Cytoskeleton staining was used to detect changes in cytoskeleton morphology. Functional assays including wound healing assays and transwell assays were used to detect the invasion and migration of cells. The effect of betulonic acid on cell invasion and migration was clearly and precisely observed by high-content imaging technology. Western blotting was used to detect the regulation of matrix metalloproteinase-related proteins and epithelial-mesenchymal transformation-related proteins. We found that betulonic acid inhibited the migration and invasion of gastric cancer cells. Therefore, betulonic acid inhibits the invasion and metastasis of gastric cancer cells by mediating cytoskeletal remodeling and regulating epithelial mesenchymal transformation.

Keywords: Celastrus orbiculatus; EMT; MMP; cytoskeleton rearrangement.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Celastrus* / chemistry
  • Cell Line, Tumor
  • Cytoskeleton / drug effects*
  • Cytoskeleton / pathology
  • Humans
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / prevention & control*
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / chemistry
  • Oleanolic Acid / pharmacology
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology

Substances

  • Antineoplastic Agents, Phytogenic
  • betulonic acid
  • Oleanolic Acid