PPAR alpha Ligands as Antitumorigenic and Antiangiogenic Agents

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor family of ligand-activated transcription factors. This subfamily is composed of three members-PPAR alpha, PPAR delta, and PPAR gamma-that differ in their cell and tissue distribution as well as in their target genes. PPAR alpha is abundantly expressed in liver, brown adipose tissue, kidney, intestine, heart, and skeletal muscle; and its ligands have been used to treat diseases such as obesity and diabetes. The recent finding that members of the PPAR family, including the PPAR alpha, are expressed by tumor and endothelial cells together with the observation that PPAR ligands regulate cell growth, survival, migration, and invasion, suggested that PPARs also play a role in cancer. In this review, we focus on the contribution of PPAR alpha to tumor and endothelial cell functions and provide compelling evidence that PPAR alpha can be viewed as a new class of ligand activated tumor suppressor gene with antiangiogenic and antitumorigenic activities. Given that PPAR ligands are currently used in medicine as hypolipidemic drugs with excellent tolerance and limited toxicity, PPAR alpha activation might offer a novel and potentially low-toxic approach for the treatment of tumor-associated angiogenesis and cancer. Copyright (C) 2008 A. Pozzi and Jorge H. Capdevila.