Peroxisome Proliferator-Activated Receptor-gamma Ligands: Potential Pharmacological Agents for Targeting the Angiogenesis Signaling Cascade in Cancer.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has currently been considered as molecular target for the treatment of human metabolic disorders. Experimental data from in vitro cultures, animal models, and clinical trials have shown that PPAR-gamma ligand activation regulates differentiation and induces cell growth arrest and apoptosis in a variety of cancer types. Tumor angiogenesis constitutes a multifaceted process implicated in complex downstream signaling pathways that triggers tumor growth, invasion, and metastasis. In this aspect, accumulating in vitro and in vivo studies have provided extensive evidence that PPAR-gamma ligands can function as modulators of the angiogenic signaling cascade. In the current review, the crucial role of PPAR-gamma ligands and the underlying mechanisms participating in tumor angiogenesis are summarized. Targeting PPAR-gamma may prove to be a potential therapeutic strategy in combined treatments with conventional chemotherapy; however, special attention should be taken as there is also substantial evidence to support that PPAR-gamma ligands can enhance angiogenic phenotype in tumoral cells.
Giaginis
Costas
C
Department of Forensic Medicine and Toxicology, Medical School, University of Athens, 11527 Athens, Greece.
Tsantili-Kakoulidou
Anna
A
Theocharis
Stamatios
S