The Roles of Dietary PPARgamma Ligands for Metastasis in Colorectal Cancer.
Dietary peroxisome proliferator-activated receptor (PPAR)gamma ligands, linoleic acid (LA) and conjugated linoleic acid (CLA), showed anticancer effects in colorectal carcinoma cells. LA is metabolized by two pathways. Cyclooxygenase (COX)-2 produces procarcinogenic prostaglandin E2, whereas 15-lipoxygenase (LOX)-1 produces PPARgamma ligands. The 15LOX-1 pathway, which is dominant in colorectal adenomas, was downregulated and inversely COX-2 was upregulated in colorectal cancer. LA and CLA inhibited peritoneal metastasis of colorectal cancer cells in nude mice. The inhibitory effect was abrogated by PPARgamma antisense treatment. A continuous LA treatment provided cancer cells quiescence. These quiescent cells formed dormant nests in nude mice administrated LA. The quiescent and dormant cells showed downregulated PPARgamma and upregulated nucleostemin. Thus, short-term exposure to dietary PPARgamma ligands inhibits cancer metastasis, whereas consistent exposure to LA provides quiescent/dormant status with possible induction of cancer stem and/or progenitor phenotype. The complicated roles of dietary PPARgamma ligands are needed to examine further.
Department of Molecular Pathology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Hiroki
H
Kuniyasu