Peroxisome proliferator activated receptor-gamma ligands induced cell growth inhibition and its influence on matrix metalloproteinase activity in human myeloid leukemia cells

Cancer Chemother Pharmacol. 2005 Oct;56(4):400-8. doi: 10.1007/s00280-005-1029-9. Epub 2005 Apr 19.

Abstract

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is one of the best characterized nuclear hormone receptors (NHRs) in the superfamily of ligand-activated transcriptional factors. PPAR-gamma ligands have recently been demonstrated to affect proliferation, differentiation and apoptosis of different cell types. The present study was undertaken to investigate PPAR-gamma ligands induced cell growth inhibition and its influence on matrix metalloproteinase MMP-9 and MMP-2 activities on leukemia K562 and HL-60 cells in vitro. The results revealed that PPAR-gamma expression was detectable in the two kinds of leukemia cells; Both 15-deoxy-delta(12,14)-prostaglandin J2(15d-PGJ2) and troglitazone (TGZ) have significant growth inhibition effects on these two kinds of leukemia cells. These two PPAR-gamma ligands could inhibit the leukemic cell adhesion to the extracellular matrix (ECM) proteins and the invasion through matrigel matrix. The expressions of MMP-9 and MMP-2 as well as their gelatinolytic activities in both HL-60 and K562 cells were inhibited by 15d-PGJ2 and TGZ significantly. We therefore conclude that PPAR-gamma ligands 15d-PGJ2 and TGZ have significant growth inhibition effects on myeloid leukemia cells in vitro, and that PPAR-gamma ligands can inhibit K562 and HL-60 cell adhesion to and invasion through ECM as well as downregulate MMP-9 and MMP-2 expressions. The data suggest that PPAR-gamma ligands may serve as potential anti-leukemia reagents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Chromans / therapeutic use*
  • Extracellular Matrix / drug effects*
  • Humans
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / enzymology
  • Metalloproteases / metabolism*
  • PPAR gamma / pharmacology
  • PPAR gamma / physiology*
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / therapeutic use
  • Thiazolidinediones / therapeutic use*
  • Troglitazone
  • Tumor Cells, Cultured

Substances

  • 15-deoxyprostaglandin J2
  • Antineoplastic Agents
  • Chromans
  • PPAR gamma
  • Thiazolidinediones
  • Metalloproteases
  • Troglitazone
  • Prostaglandin D2