Anticancer Properties of PPARalpha-Effects on Cellular Metabolism and Inflammation.
Peroxisome proliferator-activated receptors (PPARs) have lately attracted much attention as therapeutic targets. Previously, PPAR ligands were associated with the treatment of diabetes, hyperlipidemia and cardiovascular diseases, as they modulate the expression of genes regulating glucose and lipid metabolism. Recently, PPAR ligands have been also considered as potential anticancer agents, with relatively low systemic toxicity. The emerging evidence for antiproliferative, proapoptotic, antiinflammatory and potential antimetastatic properties of PPARalpha ligands prompted us to discuss possible roles of PPARalpha in tumor suppression. PPARalpha activation can target cancer cells energy balance by blocking fatty acid synthesis and by promoting fatty acid beta-oxidation. In the state of limited nutrient availability, frequently presents in the tumor microenvironment, PPARalpha cooperates with AMP-dependent protein kinase in: (i) repressing oncogenic Akt activity, (ii) inhibiting cell proliferation, and (iii) forcing glycolysis-dependent cancer cells into "metabolic catastrophe." Other potential anticancer effects of PPARalpha include suppression of inflammation, and upregulation of uncoupling proteins (UCPs), which attenuates mitochondrial reactive oxygen species production and cell proliferation. In conclusion, there are strong premises that the low-toxic and well-tolerated PPAR ligands should be considered as new therapeutic agents to fight disseminating cancer, which represents the major challenge for modern medicine and basic research.
Department of Food Biotechnology, Faculty of Food Technology, Agricultural University of Krakow, ul. Balicka 122, 31149 Krakow, Poland.
Maja
M
Grabacka
Krzysztof
K
Reiss