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

J. A. Brockman, R. A. Gupta, R. N. Dubois

Research output: Contribution to journalArticlepeer-review

301 Scopus citations

Abstract

Background and Aims: Peroxisomal proliferator-activated receptor γ (PPARγ) 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 PPARγ, activation in colorectal carcinoma cells. Methods: PPARγ 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 PPARγ in these cell lines were assessed in cellular proliferation and anchorage-independent growth assays. Flow cytometry was used to determine the effects of PPARγ activation on progression through the cell cycle. Results: PPARγ 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 PPARγ activator (BRL 49653) resulted in inhibition of anchorage-independent growth. The degree of growth inhibition correlated with the level of functional PPARγ present. Finally, activation of PPARγ resulted in G1 cell cycle arrest. Conclusions: Activation of the PPARγ 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.

Original languageEnglish (US)
Pages (from-to)1049-1055
Number of pages7
JournalGastroenterology
Volume115
Issue number5
DOIs
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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