Telmisartan as a peroxisome proliferator-activated receptor-γ ligand is a new target in the treatment of human renal cell carcinoma

Angiotensin II receptor blockers (ARBs) are widely used as hypertensive therapeutic agents. However, it has been reported that Telmisartan (a type of ARB) additionally activates peroxisome proliferator-activated receptor (PPAR)-gamma. We previously reported that PPAR-gamma ligand induced the growth arrest of renal cell carcinoma (RCC) cells through apoptosis, and that Telmisartan had the potential to inhibit prostate cancer cell growth through apoptosis. In this study, we evaluated the effects of Telmisartan and other ARBs on cell proliferation in an RCC cell line using normal proximal tubular endothelial cells (PRTECs) and the human RCC (Caki-1) cell line. The effects of Telmisartan as well as of other ARBs (Candesartan, Valsartan, Irbesartan and Losartan) on RCC cell growth were examined by MTT assay. Flow cytometry and Hoechst staining were used to determine whether or not the ARBs induced apoptosis. Telmisartan caused marked inhibition in RCC cells in a concentration- and time-dependent manner. Treatment with 100 mu M of Telmisartan induced early apoptosis and DNA fragmentation in the RCC cells, but not in the PRTECs. None of the other ARBs had an effect on cell proliferation in the RCC cells or the PRTECs. Telmisartan may mediate potent antiproliferative effects against RCC cells through PPAR-gamma. Thus, Telmisartan is a potential target for prevention and treatment in RCC.