RXRgamma and PPARgamma ligands in combination to inhibit proliferation and invasiveness in colon cancer cells

Cancer Lett. 2010 Nov 1;297(1):65-74. doi: 10.1016/j.canlet.2010.04.026. Epub 2010 May 26.

Abstract

Nuclear retinoid X receptors (RXRs) and peroxisome proliferator-activated receptors (PPARs are potential candidates as drug target for cancer prevention and treatment. We investigated if the rexinoid 6-OH-11-O-hydroxyphenantrene (IIF) potentiates the antitumoral properties of PPARgamma ligands as ciglitazone and pioglitazone, on two colon cancer cell lines: HCA-7 and HCT-116. Drugs inhibited cell growth and induced apoptosis synergistically. The combination resulted in a decrease of cyclooxigenase-2, metalloproteinases-2 and -9 expression level and activity while PPARgamma, RXRgamma and tissue inhibitors of metalloproteinase-1 and -2 expression were increased. Finally, IIF potentiated PPAR transcriptional activity by enhancement of peroxisome proliferator response elements transactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Cyclooxygenase 2 / metabolism
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • HCT116 Cells
  • Humans
  • Ligands
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness
  • PPAR gamma / agonists*
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Pioglitazone
  • Response Elements / drug effects
  • Retinoid X Receptor gamma / agonists*
  • Retinoid X Receptor gamma / metabolism
  • Thiazolidinediones / pharmacology
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Transcriptional Activation / drug effects
  • Tretinoin / analogs & derivatives
  • Tretinoin / pharmacology

Substances

  • IIF compound
  • Ligands
  • PPAR gamma
  • Retinoid X Receptor gamma
  • Thiazolidinediones
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Tretinoin
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • ciglitazone
  • Pioglitazone