Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29 human colon cancer cells

The gamma isoform of the peroxisome proliferator-activated receptor (PPAR gamma) is a nuclear receptor that regulates adipocyte differentiation. Recently it has been shown to be expressed in human colonic mucosa and cancer, but its role in colon carcinogenesis and progression is still unclear. We demonstrate that activation of PPAR gamma by ciglitazone (cig), a selective PPAR gamma ligand, induces HT-29 human colon cancer cells to undergo apoptosis. Treatment with cig also down-regulates expression of cyclooxygenase-2 (COX-2) protein. Simultaneous exposure of cells to cig and 9-cis-retinoic acid (9-cis-RA), a ligand for retinoid X receptor, results in an increased apoptotic effect and increased inhibition of COX-2 expression, compared with cells treated with either cig or 9-cis-RA alone. As COX-2 is overexpressed in human colon cancer and has been implicated in augmenting invasiveness and tumorigenecity, the ability of PPAR gamma activation to decrease COX-2 expression and induce apoptosis suggests that the PPAR gamma pathway may be considered as a therapeutic target for colon cancer.