These findings demonstrate that PSMA is widely distributed in normal tissues, and, depending on the tumors, its expression is up- or down-regulated, or unchanged. The broad distribution of PSMA may make it suitable for the diagnosis and therapy of a wide variety of tumors.
Abstract. Angiotensin II receptor blockers (ARBs) are widely used as hypertensive therapeutic agents. In addition, studies have provided evidence that ARBs have the potential to inhibit the growth of several types of cancer cells. It was reported that telmisartan (a type of ARB) has peroxisome proliferatoractivated receptor (PPAR)-γ activation activity. We previously reported that the PPAR-γ ligand induces growth arrest in human urological cancer cells through apoptosis. In this study, we evaluated the effects of telmisartan and other ARBs on cell proliferation in renal cell carcinoma (RCC), bladder cancer (BC), prostate cancer (PC) and testicular cancer (TC) cell lines. The inhibitory effects of telmisartan and other ARBs (candesartan, valsartan, irbesartan and losartan) on the growth of the RCC, BC, PC and TC cell lines was investigated using an MTT assay. Flow cytometry and Hoechst staining were used to determine whether the ARBs induced apoptosis. Telmisartan caused marked growth inhibition in the urological cancer cells in a dose-and time-dependent manner. Urological cancer cells treated with 100 µM telmisartan underwent early apoptosis and DNA fragmentation. However, the other ARBs had no effect on cell proliferation in any of the urological cancer cell lines. Telmisartan may mediate potent anti-proliferative effects in urological cancer cells through PPAR-γ. Thus, telmisartan is a potent target for the prevention and treatment of human urological cancer.
IntroductionAngiogenetic factors play key roles in urological as well as other types of cancer. In recent years, the expression of angiogenic factors in solid human tumors has been widely reported (1). Growth factors secreted by tumor cells, such as fibroblast and transforming growth factors, increase neovascularization in vivo and in vitro (2). Studies have demonstrated that peroxisome proliferator-activated receptor (PPAR)-γ ligands inhibit the growth of cancer cells in vitro and in vivo (3). PPAR-γ, a nuclear hormone receptor, provides a strong link between lipid metabolism and the regulation of gene transcription (4). PPAR-γ acts in the adipose tissue and promotes lipogenesis under anabolic conditions. Recently, the receptor has also been implicated in inflammation and carcinogenesis. Significant evidence from many experimental systems suggests that PPAR-γ plays an important role in carcinogenesis.Angiotensin II is known as a key biological peptide in the renin-angiotensin system, which regulates blood pressure and renal hemodynamics, and angiotensin II receptor blockers (ARBs) are widely used as anti-hypertensive drugs (5). It is well known that angiogenesis is essential for tumor progression and metastasis (6,7). Several studies have shown that angiotensin II induces neovascularization and that ARBs inhibit vascular endothelial growth factor (VEGF) production (8,9). Benson et al discovered a structural resemblance between telmisartan (a type of ARB) and a PPAR-γ ligand approved for the treatment of type II diabetes, and reported that telmisartan has...
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