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, 2008, 358052

Omega-3 Fatty Acids and PPARgamma in Cancer


Omega-3 Fatty Acids and PPARgamma in Cancer

Iris J Edwards et al. PPAR Res.


Omega-3 (or n-3) polyunsaturated fatty acids (PUFAs) and their metabolites are natural ligands for peroxisome proliferator receptor activator (PPAR)gamma and, due to the effects of PPARgamma 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 PPARgamma activation. The differential activation of PPARgamma and PPARgamma-regulated genes by specific dietary fatty acids may be central to their distinct roles in cancer. This review summarizes studies relating PUFAs to PPARgamma and cancer and offers a new paradigm relating an n-3 PUFA through PPARgamma to the expression of the cell surface proteoglycan, syndecan-1, and to the death of cancer cells.


Figure 1
Figure 1
Structures of unsaturated fatty acids: oleic acid (n-9 monounsaturated), linoleic acid and arachidonic acid (n-6 polyunsaturated), α-linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid (n-3 polyunsaturated ). The “n” numbers are counted from the methyl or omega terminus.
Figure 2
Figure 2
The elongation-desaturation pathway for the metabolism of n-6 and n-3 polyunsaturated fatty acids.
Figure 3
Figure 3
The cellular metabolism of LA, AA, and DHA to more potent activators of PPARγ. ODE is octadecaenoate; HETE is hydroxy-eicosatetraenoate; ETE is eicosatetraenoate; PG is prostaglandin.
Figure 4
Figure 4
The syndecan-1 pathway for n-3 PUFA induction of apoptosis. Dashed lines indicate that effects may be indirect with involvement of other metabolites and signaling molecules.

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