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Inhibition of cell proliferation by potential peroxisome proliferator-activated receptor (PPAR) gamma agonists and

Michael A Lea1, Monali Sura, Charles Desbordes

  • 1Department of Biochemistry and Molecular Biology, UMDNJ - New Jersey Medical School, Newark, New Jersey 07103, USA. lea@umdnj.edu

Anticancer Research
|November 3, 2004
PubMed

Insights

PPAR gamma antagonists did not block 4-phenylbutyrate

Area of Science:

  • Cell biology
  • Molecular biology
  • Cancer research

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor involved in various cellular processes.
  • PPARγ ligands, including agonists and antagonists, are being investigated for their role in cell proliferation and cancer.
  • 4-phenylbutyrate, a PPARγ ligand, also induces histone acetylation, suggesting alternative mechanisms of action.

Purpose of the Study:

  • To investigate whether potential PPARγ antagonists could counteract the cell proliferation inhibition caused by 4-phenylbutyrate.
  • To explore the effects of PPARγ agonists and antagonists on cancer cell proliferation and lipid accumulation.
  • To determine the role of PPARγ and histone acetylation in the cellular effects of 4-phenylbutyrate.

Main Methods:

  • Utilized DS19 mouse erythroleukemia cells and human cancer cell lines (PC3, Caco-2, T47D).
  • Treated cells with PPARγ agonists (4-phenylbutyrate, rosiglitazone, ciglitazone, GW1929) and antagonists (BADGE, GW9662, PD068235, diclofenac).
  • Assessed cell proliferation via thymidine incorporation and observed lipid accumulation.

Main Results:

  • Both PPARγ agonists and antagonists inhibited cell proliferation across various cancer cell lines and NIH3T3 cells.
  • Combined treatments showed additive inhibitory effects on cell proliferation.
  • Lipid accumulation was observed in T47D cells treated with 4-phenylbutyrate and both agonist/antagonist types.

Conclusions:

  • Potential PPARγ antagonists may not reverse the growth-inhibitory effects of PPARγ ligands.
  • PPARγ antagonists themselves can exhibit growth-inhibitory properties.
  • The precise mechanisms by which 4-phenylbutyrate affects cell proliferation, whether via PPARγ or histone acetylation, require further investigation.

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