Anti-tumour effects of beta-sitosterol are mediated by AMPK/PTEN/HSP90 axis in AGS human gastric adenocarcinoma cells and xenograft mouse models

Biochem Pharmacol. 2018 Jun:152:60-70. doi: 10.1016/j.bcp.2018.03.010. Epub 2018 Mar 17.


We investigated the anti-cancer effects of beta-sitosterol (BS), a plant-derived sterol in AGS human gastric adenocarcinoma cells and xenograft mouse models. BS significantly reduced cell viability by inducing apoptosis in AGS adenocarcinoma cells. This was accompanied by the formation of apoptotic bodies, as detected by Annexin V, caspase 3/7 activity, and MitoPotential assay. BS stimulated phosphatase and tensin homolog (PTEN) and phospho-AMP-activated protein kinase (p-AMPK) expression. Pharmacological inhibitors or siRNA were used to further analyse the relationship between the two proteins. AMPK was found to represent a likely upstream regulator of PTEN. Additionally, two-dimensional gel electrophoresis was used to identify related proteins in the treatment of BS. The decrease of Hsp90 protein by BS was observed. Induction of PTEN protein and reduction of Hsp90 was mediated by AICAR, an AMPK activator, indicating that AMPK is necessary for PTEN and Hsp90 expression. Additionally, BS was found to be effective through the regulation of cancer biomarker. Furthermore, BS suppressed tumour growth without toxicity in the AGS xenograft mouse models-. Taken together, the present results demonstrate that BS exerts anti-cancer effects in AGS cells and xenograft mouse models by mediating AMPK, PTEN, and Hsp90.

Keywords: AMP-activated protein kinase; Beta-sitosterol; Human gastric adenocarcinoma cells; Phosphatase and tensin homolog.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenylate Kinase / genetics
  • Adenylate Kinase / metabolism
  • Animals
  • Apoptosis
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • HSP90 Heat-Shock Proteins / genetics
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Hypolipidemic Agents / pharmacology
  • Male
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / drug therapy*
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Sitosterols / pharmacology*
  • Stomach Neoplasms / drug therapy*


  • Biomarkers, Tumor
  • HSP90 Heat-Shock Proteins
  • Hypolipidemic Agents
  • Sitosterols
  • gamma-sitosterol
  • Adenylate Kinase
  • PTEN Phosphohydrolase