Fatostatin suppresses growth and enhances apoptosis by blocking SREBP-regulated metabolic pathways in endometrial carcinoma

Oncol Rep. 2018 Apr;39(4):1919-1929. doi: 10.3892/or.2018.6265. Epub 2018 Feb 13.

Abstract

Fatostatin, a chemical inhibitor of the sterol regulatory element‑binding protein (SREBP) pathway, has been reported to possess high antitumor activity against prostate and pancreatic cancer. The main aim of the present study was to investigate the effects and mechanism of fatostatin in endometrial carcinoma (EC). In the present study, we determined that fatostatin inhibited EC cell viability and colony formation capacity, decreased the invasive and migratory capacities of EC cells, induced EC cell cycle arrest at the G2/M phase and stimulated caspase‑mediated apoptosis of EC cells. In addition, fatostatin significantly decreased the protein expression levels of nuclear SREBPs and their downstream genes and increased the protein expression levels of cleaved caspase‑9, caspase‑3 and PARP in EC cells. In addition, the mRNA expression levels of SREBP‑controlled downstream genes were also significantly downregulated. The quantification assays of fatty acids and total cholesterol revealed that the levels of free fatty acids and total cholesterol in EC cells were decreased. The present study indicated that fatostatin exhibited antitumor effects by blocking SREBP‑regulated metabolic pathways and inducing caspase‑mediated apoptosis in EC and may be a potent therapeutic strategy for the treatment of EC.

MeSH terms

  • Apoptosis / drug effects
  • Caspases / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Metabolic Networks and Pathways / drug effects
  • Pyridines / administration & dosage*
  • Stem Cells / drug effects
  • Sterol Regulatory Element Binding Proteins / antagonists & inhibitors
  • Sterol Regulatory Element Binding Proteins / genetics*
  • Thiazoles / administration & dosage*

Substances

  • Pyridines
  • Sterol Regulatory Element Binding Proteins
  • Thiazoles
  • fatostatin
  • Caspases