Targeting PPARγSignaling Cascade for the Prevention and Treatment of Prostate Cancer

Abstract

The peroxisome proliferator-activated receptor-gamma (PPARγ) is a member of the hormone-activated nuclear receptor superfamily. PPARγcan be activated by a diverse group of agents, such as endogenous polyunsaturated fatty acids, 15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2), and thiazolidinedione (TZD) drugs. PPARγinduces antiproliferative, antiangiogenic, and prodifferentiation pathways in several tissue types, thus making it a highly useful target for downregulation of carcinogenesis. These TZD-derived novel therapeutic agents, alone or in combination with other anticancer drugs, have translational relevance in fostering effective strategies for cancer treatment. TZDs have been proven for antitumor activity in a wide variety of experimental cancer models, bothin vitroandin vivo, by affecting the cell cycle, inducing cell differentiation and apoptosis, as well as by inhibiting tumor angiogenesis. Angiogenesis inhibition mechanisms of TZDs include direct inhibition of endothelial cell proliferation and migration, as well as reduction in tumor cell vascular endothelial growth factor production. In prostate cancer, PPARγligands such as troglitazone and 15d-PGJ2have also shown to inhibit tumor growth. This paper will focus on current discoveries in PPARγactivation, targeting prostate carcinogenesis as well as the role of PPARγas a possible anticancer therapeutic option. Here, we review PPARγas an antitumor agent and summarize the antineoplastic effects of PPARγagonists in prostate cancer.