Omega‐3 Fatty Acids and PPARγ in Cancer

Abstract

Omega-3 (or n-3) polyunsaturated fatty acids (PUFAs) and their metabolites are natural ligands for peroxisome proliferator receptor activator (PPAR)γ and, due to the effects of PPARγ on cell proliferation, survival, and differentiation, are potential anticancer agents. Dietary intake of omega-3 PUFAs has been associated with a reduced risk of certain cancers in human populations and in animal models. In vitro studies have shown that omega-3 PUFAs inhibit cell proliferation and induce apoptosis in cancer cells through various pathways but one of which involves PPARγ activation. The differential activation of PPARγ and PPARγ-regulated genes by specific dietary fatty acids may be central to their distinct roles in cancer. This review summarizes studies relating PUFAs to PPARγ and cancer and offers a new paradigm relating an n-3 PUFA through PPARγ to the expression of the cell surface proteoglycan, syndecan-1, and to the death of cancer cells.

Interaction of brain fatty acid-binding protein with the polyunsaturated fatty acid environment as a potential determinant of poor prognosis in malignant glioma

“…Our results indicating that COX-2 is up-regulated and PPARγ is down-regulated, in FABP7-positive U87 cells cultured in an AA-rich environment, are in keeping with COX-2 being down-regulated by PPARγ in DHA-treated malignant glioma [18]. It is worth mentioning that some DHA metabolites such as 17-hydroxy DHA are more potent activators of PPARγ than DHA itself [112,114] and therefore could contribute to the DHA effect.…”

Maintaining hepatocyte differentiation in vitro through co-culture with hepatic stellate cells

“…Nonetheless, it should well be considered that the active component in the lipid extract was not vitamin A alone, since the lipid droplets of HSCs also contain triglycerides, cholesterol and phospholipids (Yamada et al 1987;Moriwaki et al 1988). The antiproliferative and differentiative action of vitamin A has been well investigated (Fields et al 2007); more recently unsaturated fatty acids have been recognised as important signals in diverse processes such as differentiation, development and proliferation (Tontonoz and Spiegelman 2008;Edwards and O'Flaherty 2008). The question remains as to how lipids and especially vitamin A from the intracellular HSC stores reach the neighbouring hepatocytes.…”

The ω3‐polyunsaturated fatty acid derivatives AVX001 and AVX002 directly inhibit cytosolic phospholipase A2 and suppress PGE2 formation in mesangial cells

“…***P < 0.001 considered statistically significant when compared with the control values; # P < 0.05, ### P < 0.001 when compared with the IL-1b-stimulated values. diseases and even certain forms of cancer (Calder, 2005;Calon and Cole, 2007;Edwards and O'Flaherty, 2008).…”

“…diseases and even certain forms of cancer (Calder, 2005;Calon and Cole, 2007;Edwards and O'Flaherty, 2008). Various possibilities for the mechanism of these antiinflammatory effects were forwarded.…”

“…***P < 0.001 considered statistically significant when compared with the control values; # P < 0.05, ### P < 0.001 when compared with the IL-1b-stimulated values. diseases and even certain forms of cancer (Calder, 2005;Calon and Cole, 2007;Edwards and O'Flaherty, 2008).Various possibilities for the mechanism of these antiinflammatory effects were forwarded. For example, an increased incorporation of w3-PUFA species into phospholipids may occur at the expense of arachidonic acid.…”