A novel PPAR alpha/gamma dual agonist inhibits cell growth and induces apoptosis in human glioblastoma T98G cells

Acta Pharmacol Sin. 2004 Oct;25(10):1312-9.

Abstract

Aim: To examine the effect of a novel peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual agonist TZD18 on cell proliferation and apoptosis in human glioblastoma T98G cells and its possible mechanism.

Methods: RT-PCR, MTT, TUNEL, Flow cytometry, and Western blot analysis were employed.

Results: TZD18 inhibited the growth of T98G cells in a concentration-dependent manner, which was associated with a G1 to S cell cycle arrest. Besides, significant apoptosis was induced after treatment with a non-toxic dose of TZD18. During the process, the expression of Bcl-2 protein was down-regulated, while that of Bax and p27kip proteins was up-regulated, and the activity of caspase-3 was elevated. However, this effect appeared to be PPARalpha and PPARgamma independent since their antagonists could not reverse this effect.

Conclusions: TZD18, a novel PPARalpha/gamma dual agonist, inhibited cell growth and induce apoptosis in human glioblastoma T98G cells in vitro, indicating a therapeutic potential for TZD18 in the treatment of glioblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Caspase 3
  • Caspases / metabolism
  • Cell Cycle / drug effects
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinase Inhibitor p27
  • Female
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Humans
  • PPAR alpha / agonists*
  • PPAR alpha / metabolism
  • PPAR gamma / agonists*
  • PPAR gamma / metabolism
  • Phenyl Ethers / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Thiazolidinediones / pharmacology*
  • Tumor Suppressor Proteins / metabolism
  • bcl-2-Associated X Protein

Substances

  • 5-(3-(3-(4-phenoxy-2-propylphenoxy)propoxy)phenyl)-2,4-thiazolidinedione
  • BAX protein, human
  • Cell Cycle Proteins
  • PPAR alpha
  • PPAR gamma
  • Phenyl Ethers
  • Proto-Oncogene Proteins c-bcl-2
  • Thiazolidinediones
  • Tumor Suppressor Proteins
  • bcl-2-Associated X Protein
  • Cyclin-Dependent Kinase Inhibitor p27
  • CASP3 protein, human
  • Caspase 3
  • Caspases