Ligands for
peroxisome proliferator-activated receptor-beta/delta (
PPARbeta/delta) increase skeletal muscle
fatty acid catabolism, improve
insulin sensitivity, increase serum
high-density lipoprotein cholesterol, elicit anti-inflammatory activity and induce terminal differentiation. Contradictory findings are also reported suggesting that
PPARbeta/delta
ligands potentiate
tumorigenesis by increasing cell proliferation, by inhibiting apoptosis through phosphorylation of Akt and by increasing
cyclooxygenase-2 (COX2) and
vascular endothelial growth factor (
VEGF) expression. The contradictory findings could be due to differences in the model system (
cancer cell line versus in vivo), differences in cell culture conditions (with and without serum) or differences in
ligands. The present study examined the effect of two different
PPARbeta/delta
ligands (
GW0742 and
GW501516) in human
cancer cell lines (HT29, HCT116, LS-174T, HepG2 and HuH7) cultured in the presence or absence of serum and compared in vitro analysis with in vivo analysis. Neither
PPARbeta/delta
ligand increased cell growth or phosphorylation of Akt and no increase in the expression of
VEGF or COX2 were detected in any
cancer cell line in the presence or absence of serum. Similarly, liver, colon and colon
polyps from mice administered these
PPARbeta/delta
ligands in vivo did not exhibit changes in these markers. Results from these studies demonstrate that serum withdrawal and/or differences in
ligands do not underlie the disparity in responses reported in the literature. The quantitative nature of the present findings are inconsistent with the hypothesis that
cancer cell lines respond differentially as compared with normal cells, and provide further evidence that
PPARbeta/delta
ligands do not potentiate
tumorigenesis.