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

Abstract

Abstract. 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)-Á. We previously reported that PPAR-Á 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 μM 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-Á. Thus, Telmisartan is a potential target for prevention and treatment in RCC.

Telmisartan Induces Growth Inhibition, DNA Double-Strand Breaks and Apoptosis in Human Endometrial Cancer Cells

“…It has also been demonstrated that telmisartan induced apoptosis and DNA fragmentation in human urological cancer [8], [9], [29]. Here we found that treatment with telmisartan significantly increased the number of apoptotic cells in all endometrial carcinoma cell lines studied.…”

Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest

“…Telmisartan has been shown to inhibit cell proliferation by inducing apoptosis in various cancer cell lines, namely, prostate ( 8 ), renal ( 9 ), endometrial ( 6 ) and colon ( 10 ) cancer lines. To determine whether telmisartan induced apoptosis, HuCCT-1 cells were treated with or without 100 µ M telmisartan and analyzed using Annexin V-FITC/PI staining and measuring the levels of cCK18, but it did not induce apoptosis and cell death after telmisartan-treatment in HuCCT-1 cells.…”

“…It inhibited the growth of adult T-cell leukemia cell ( 5 ), endometrial ( 6 ), and gastric cancer cells ( 7 ) in several studies. The main mechanism associated with antitumor effect by telmisartan treatment has been shown to inhibit cell proliferation by inducing apoptosis in various cancer cell lines, including prostate ( 8 ), renal ( 9 ), endometrial ( 6 ) and colon ( 10 ) cancer lines. More recently, telmisartan induced cell cycle arrest in hematologic and non-hematologic malignancies including our study ( 5 , 11 ).…”

The angiotensin II type 1 receptor antagonist telmisartan inhibits cell proliferation and tumor growth of esophageal adenocarcinoma via the AMPKα/mTOR pathwayin vitroandin vivo

“…Telmisartan has been shown to inhibit cell proliferation by inducing apoptosis in various cancer cell lines, including endometrial [10], prostate [19], renal [20], and colon [21] cancer lines. To determine whether telmisartan induced apoptosis, we treated EAC cells with or without 100 μM telmisartan for 24 and 48 h and analyzed the cells using flow cytometry.…”

“…PPAR-γ activation inhibits cell growth in several cancers [15–18]. Additionally, telmisartan inhibits the proliferation of various cancer cell types, including prostate [19], renal [20] and colon [21] cancer cells, by inducing apoptosis.…”