Effects of Cynaroside on Cell Proliferation, Apoptosis, Migration and Invasion though the MET/AKT/mTOR Axis in Gastric Cancer

Int J Mol Sci. 2021 Nov 9;22(22):12125. doi: 10.3390/ijms222212125.

Abstract

The Chinese medicine monomer cynaroside (Cy) is a flavonoid glycoside compound that widely exists in plants and has a variety of pharmacological effects, such as its important role in the respiratory system, cardiovascular system and central nervous system. Studies have reported that Cy has varying degrees of anticancer activity in non-small cell lung cancer, cervical cancer, liver cancer, esophageal cancer and other cancers. However, there are no relevant reports about its role in gastric cancer. The MET/AKT/mTOR signaling pathway plays important roles in regulating various biological processes, including cell proliferation, apoptosis, autophagy, invasion and tumorigenesis. In this study, we confirmed that Cy can inhibit the cell growth, migration and invasion and tumorigenesis in gastric cancer. Our finding shows that Cy can block the MET/AKT/mTOR axis by decreasing the phosphorylation level of AKT, mTOR and P70S6K. Therefore, the MET/AKT/mTOR axis may be an important target for Cy. In summary, Cy has anti-cancer properties and is expected to be a potential drug for the treatment of gastric cancer.

Keywords: MET; cell proliferation; cynaroside; gastric cancer; migration and invasion.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glucosides / pharmacology*
  • Humans
  • Luteolin / pharmacology*
  • Medicine, Chinese Traditional
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-met / genetics*
  • Ribosomal Protein S6 Kinases, 70-kDa / genetics
  • Signal Transduction / drug effects
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • TOR Serine-Threonine Kinases / genetics*

Substances

  • Glucosides
  • luteolin-7-glucoside
  • MTOR protein, human
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • Luteolin