A-24, a steroidal saponin from Allium chinense, induced apoptosis, autophagy and migration inhibition in p53 wild-type and p53-deficient gastric cancer cells

Chem Biol Interact. 2021 Oct 1:348:109648. doi: 10.1016/j.cbi.2021.109648. Epub 2021 Sep 8.

Abstract

Allium chinense is a vegetable with nutrition and unique flavor, and it is used as traditional Chinese medicine. We previously reported that the active compound A-24 induces apoptosis and autophagy in p53 wild-type gastric cancer cells through the PI3K/Akt/mTOR pathway. Our present work indicates that A-24 also has a significant proliferation inhibition effect on p53-deficient KATO-III cells, and the p53 status did not affect A-24 induced migration inhibition, but negatively controlled the occurrence of autophagy. We also found that the accumulation of reactive oxygen species (ROS) mediated A-24 induced apoptosis is p53-independent. Besides, p-Akt was not downregulated by A-24 in p53-deficient gastric cancer cells. Taken together, our results indicate that A-24 induced apoptosis and autophagy via the ROS-PI3K/Akt/mTOR pathway in p53 wild-type gastric cancer cells and through the ROS-mTOR pathway in p53-deficient gastric cancer cells. Our study recommended A-24 as a promising future phytotherapeutic candidate for gastric cancer treatment.

Keywords: Allium chinense; Autophagy; ROS; Saponin; p53.

MeSH terms

  • Allium / chemistry*
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Humans
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Saponins / chemistry
  • Saponins / pharmacology*
  • Signal Transduction / drug effects
  • Stomach Neoplasms / pathology*
  • Tumor Suppressor Protein p53 / deficiency
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Reactive Oxygen Species
  • Saponins
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-akt