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

Background & Aims: Peroxisomal proliferator-activated receptor gamma (PPAR gamma) 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 PPAR gamma activation in colorectal carcinoma cells. Methods: PPAR gamma 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 PPAR gamma in these cell lines were assessed in cellular proliferation and anchorage-independent growth assays. Flow cytometry was used to determine the effects of PPAR gamma activation on progression through the cell cycle. Results: PPAR gamma was expressed in ail 4 colon cancer cell lines examined and was transcriptionally functional in 3 of the 4. Treatment of these cells with a selective PPAR gamma activator (BRL 49653) resulted in inhibition of anchorage-independent growth. The degree of growth inhibition correlated with the level of functional PPAR gamma present. Finally, activation of PPAR gamma resulted in G(1) cell cycle arrest. Conclusions: Activation of the PPAR gamma 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.