Background: Prostate cancer (PCa) and Type 2 diabetes (T2D) are two major health risks that often occur concurrently in men. Studies predict that diabetic PCa patients have a reduced risk of PCa progression, while other studies show contradicting data. This impedes unraveling the connection between PCa with T2D. Besides other drugs, Peroxisome Proliferator-Activated Receptor (PPAR) agonists have been applied as T2D medication in patients. In publicly available patient datasets high PPARγ expression correlated with advanced PCa and worse survival outcomes. Aim: We investigated the effect of PPAR agonists Bezafibrate (PPARα), Tesaglitazar (PPARα/γ), and Pioglitazone (PPARγ) on PCa tumorigenesis using primary PCa 22RV1 and metastatic PC3 cells. To get an unbiased view on the proteome repertoire of primary and metastatic PCa cells, we analysed their proteome at basal culture conditions and following treatment with PPAR agonists Bezafibrate, Tesaglitazar, and Pioglitazone. As compared to vitality assays, we chose a relatively short (24h) treatment period, assuming that early proteome alterations might provide mechanistic insight to explain the effect of PPAR agonists on vitality and proliferation.