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Targeting Peroxisome Proliferator-Activated Receptor-β/δ (PPARβ/δ) for Cancer Chemoprevention
Jeffrey M Peters1, Pei-Li Yao1, Frank J Gonzalez2
1Department of Veterinary and Biomedical Sciences and The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802 USA.
Abstract:
The role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in cancer remains contentious due in large part to divergent publications indicating opposing effects in different rodent and human cell culture models. During the past 10 years, some facts regarding PPARβ/δ in cancer have become clearer, while others remain uncertain. For example, it is now well accepted that (1) expression of PPARβ/δ is relatively lower in most human tumors as compared to the corresponding non-transformed tissue, (2) PPARβ/δ promotes terminal differentiation, and (3) PPARβ/δ inhibits pro-inflammatory signaling in multiple in vivo models. However, whether PPARβ/δ is suitable to target with natural and/or synthetic agonists or antagonists for cancer chemoprevention is hindered because of the uncertainty in the mechanism of action and role in carcinogenesis. Recent findings that shed new insight into the possibility of targeting this nuclear receptor to improve human health will be discussed.
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