The ligands of peroxisome proliferator-activated receptor (PPAR) gamma inhibit growth of human esophageal carcinoma cells through induction of apoptosis and cell cycle arrest

Anticancer Res. 2004 May-Jun;24(3a):1409-16.

Abstract

In the present study, we examined the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and the growth-inhibitory effects of Troglitazone and Pioglitazone, selective ligands for PPARgamma, using a series of human esophageal carcinoma cell lines (TE-1, -3, -7, -8, -12 and -13). PPARgamma expression was detected in all six human esophageal carcinoma cell lines. The esophageal carcinoma cell line TE-13 showed marked growth inhibition in response to Troglitazone and Pioglitazone. Flow cytometry performed on TE-13 cells exposed to Troglitazone showed that the cell cycle was arrested at the G1-phase. This result was confirmed by the finding of reduced cyclin D and cyclin E expression by Western blot analysis. DNA ladder formation was also detected, as was the induction of apoptosis-related proteins. Our results suggested that Troglitazone inhibited the growth of human esophageal carcinoma cell lines via G1 arrest and apoptosis and that PPARgamma ligands should be considered as possible target molecules in the treatment of human esophageal carcinomas.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Blotting, Western
  • Cell Cycle / drug effects
  • Cell Cycle Proteins / biosynthesis
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Chromans / pharmacology*
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Ligands
  • Pioglitazone
  • Receptors, Cytoplasmic and Nuclear / biosynthesis*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Thiazolidinediones / pharmacology*
  • Transcription Factors / biosynthesis*
  • Transcription Factors / metabolism
  • Troglitazone

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • Chromans
  • Ligands
  • Receptors, Cytoplasmic and Nuclear
  • Thiazolidinediones
  • Transcription Factors
  • Troglitazone
  • Pioglitazone