Activation of PPARgamma leads to inhibition of anchorage-independent growth of human colorectal cancer cells

Gastroenterology. 1998 Nov;115(5):1049-55. doi: 10.1016/s0016-5085(98)70072-1.


Background & aims: Peroxisomal proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor that provides a direct link between fatty acid metabolism and control of gene transcription. The objective of this study was to determine the biological effect(s) of PPARgamma activation in colorectal carcinoma cells.

Methods: PPARgamma expression and activity were measured in 4 human colon cancer cell lines using reverse-transcription polymerase chain reaction, immunoprecipitation and immunoblotting, and transient reporter gene assays. The effects of activated PPARgamma in these cell lines were assessed in cellular proliferation and anchorage-independent growth assays. Flow cytometry was used to determine the effects of PPARgamma activation on progression through the cell cycle.

Results: PPARgamma was expressed in all 4 colon cancer cell lines examined and was transcriptionally functional in 3 of the 4. Treatment of these cells with a selective PPARgamma activator (BRL 49653) resulted in inhibition of anchorage-independent growth. The degree of growth inhibition correlated with the level of functional PPARgamma present. Finally, activation of PPARgamma resulted in G1 cell cycle arrest.

Conclusions: Activation of the PPARgamma pathway in colon cancer cells has potent antiproliferative effects, suggesting that this nuclear hormone receptor may provide a novel target for prevention and treatment of colorectal cancer in humans.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Cell Division / physiology
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • G1 Phase / drug effects
  • Humans
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Rosiglitazone
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / agonists
  • Transcription Factors / physiology*
  • Tumor Cells, Cultured / drug effects


  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Rosiglitazone