Inhibition of human lung cancer cell growth by the peroxisome proliferator-activated receptor-gamma agonists through induction of apoptosis

Biochem Biophys Res Commun. 2000 Apr 13;270(2):400-5. doi: 10.1006/bbrc.2000.2436.

Abstract

Peroxisome proliferator-activated receptors (PPARs), members of the nuclear hormone receptors superfamily, have an important regulatory role in adipogenesis and inflammation. PPAR-gamma ligands induce terminal differentiation and growth inhibition of human breast cancer cells and prostatic cancer cells. In this study, we demonstrated that PPAR-gamma, but not PPAR-alpha, was expressed in human lung cancer cell lines by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. We also found that the synthetic PPAR-gamma agonist thiazolidinedione compounds (troglitazone) and the endogenous PPAR-gamma ligand, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), inhibited the growth of human lung cancer cells through the induction of apoptosis. However, PPAR-alpha agonist (bezafibrate) and other prostanoids (PGE(2), PGF(2alpha)) did not induce apoptosis. These findings suggest that PPAR-gamma may play an important role in the pathogenesis of lung cancer and that PPAR-gamma agonist may be useful therapeutic agents in the treatment of human lung cancer.

MeSH terms

  • Apoptosis / drug effects*
  • Base Sequence
  • Cell Division / drug effects*
  • Chromans / pharmacology*
  • DNA Primers
  • Humans
  • Lung Neoplasms / pathology*
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / pharmacology
  • RNA, Messenger / genetics
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Thiazoles / pharmacology*
  • Thiazolidinediones*
  • Transcription Factors / agonists*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Troglitazone
  • Tumor Cells, Cultured

Substances

  • 15-deoxy-delta(12,14)-prostaglandin J2
  • Chromans
  • DNA Primers
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Troglitazone
  • Prostaglandin D2