Troglitazone, a peroxisome proliferator-activated receptor gamma ligand, induces growth inhibition and apoptosis of HepG2 human liver cancer cells

World J Gastroenterol. 2008 Apr 14;14(14):2168-73. doi: 10.3748/wjg.14.2168.

Abstract

Aim: To examine the effect of troglitazone, a peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand, on the proliferation and apoptosis of human liver cancer cells.

Methods: Liver cancer cell line HepG2 was cultured and treated with troglitazone. Cell proliferation was detected by 3-(4-,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay; apoptosis was detected by flow cytometry and terminal deoxynucleotidyl transferase-mediated nick end labeling of DNA fragmentation sites (TUNEL) assay; and apoptosis-related protein was detected by immunocytochemistry and Western blotting.

Results: Troglitazone inhibited growth and induced apoptosis of HepG2 cells in a dose-dependent manner, and induced activation of caspase-3 expression. Troglitazone not only drove apoptosis-inhibiting factor survivin to translocate incompletely from the nucleus to the cytoplasm, but also inhibited expression of survivin, while it did not affect expression of apoptosis-promoting factor Bax.

Conclusion: PPAR gamma ligands inhibit growth and induce apoptosis of liver cancer cells, and may have applications for the prevention and treatment of liver cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Caspase 3 / biosynthesis
  • Cell Nucleus / metabolism
  • Chromans / pharmacology*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • In Situ Nick-End Labeling
  • Ligands
  • Models, Biological
  • PPAR gamma / metabolism*
  • Protein Transport
  • Tetrazolium Salts / pharmacology
  • Thiazoles / pharmacology
  • Thiazolidinediones / pharmacology*
  • Troglitazone

Substances

  • Antineoplastic Agents
  • Chromans
  • Ligands
  • PPAR gamma
  • Tetrazolium Salts
  • Thiazoles
  • Thiazolidinediones
  • Caspase 3
  • thiazolyl blue
  • Troglitazone