The effect of peroxisome proliferator-activated receptor-γ ligand on urological cancer cells

Yoshimura, Rikio; Matsuyama, Masahide; Hase, Tsunao; Tsuchida, Kenji; Kuratsukuri, Katsuyuki; Kawahito, Yutaka; Sano, Hajime; Segawa, Yoshihiro; Nakatani, Tatsuya

doi:10.3892/ijmm.12.6.861

Cited by 24 publications

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“…The extent and intensity of PPAR-γ expression in urological cancer tissues were greater than in normal urological tissues. PPAR-γ ligands strongly induced early apoptosis in urological cancer cells as determined by flow cytometry and Hoechst staining (11)(12)(13)(14)(15). In this study, only telmisartan had a direct toxicity through apoptosis.…”

Section: Discussionmentioning

confidence: 79%

“…Our previous research revealed the expression of PPARs in human urological cancers and investigated the administration of PPAR-γ ligands as an anti-cancer therapy (11)(12)(13)(14)(15). With this background, the present study aimed to evaluate the inhibitory effect of telmisartan on human renal cell carcinoma (RCC), bladder cancer (BC), prostate cancer (PC) and testicular cancer (TC) cell lines, and to determine whether telmisartan induces apoptosis in such cells.…”

Section: Introductionmentioning

confidence: 99%

“…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 PPAR-γ action (10).Our previous research revealed the expression of PPARs in human urological cancers and investigated the administration of PPAR-γ ligands as an anti-cancer therapy (11)(12)(13)(14)(15). With this background, the present study aimed to evaluate the inhibitory effect of telmisartan on human renal cell carcinoma (RCC), bladder cancer (BC), prostate cancer (PC) and testicular cancer (TC) cell lines, and to determine whether telmisartan induces apoptosis in such cells.…”

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confidence: 99%

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Telmisartan inhibits human urological cancer cell growth through early apoptosis

Matsuyama

Funao²,

Kuratsukuri³

et al. 2010

Experimental and Therapeutic Medicine

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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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Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Telmisartan inhibits human urological cancer cell growth through early apoptosis

Matsuyama

Funao²,

Kuratsukuri³

et al. 2010

Experimental and Therapeutic Medicine

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“…Consequently, in the present study we aimed to evaluate the inhibitory effect of Telmisartan on human RCC cells, and to determine whether or not it induces apoptosis in these cells. Our findings elucidate PPAR expression in urological cancer and indicate that the administration of PPAR-Á ligand may serve as a form of anticancer therapy (15)(16)(17)(18)(19). Cell cultures.…”

Section: Telmisartan As a Peroxisome Proliferator-activated Receptor-mentioning

confidence: 99%

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

Funao

Matsuyama²,

Kawahito³

et al. 2009

Mol Med Rep

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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.

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“…They have a lethal effect on adipocyte differentiation on the gene responsible for adipocyte lipid-binding protein (aP2), phosphoenolpyruvate carboxykinase, acyl-CoA synthase, and lipoprotein lipase as well as induce negative signal for other tissues to accumulate triglycerides (TG) [59]. Natural anti-inflammatory ligand 15d-PGJ2 [60] and nonsteroidal anti-inflammatory agents (NSAIDs) including ibuprofen, fenoprofen and indomethacin [61] have PPAR-γ agonistic effect. These agents induce anti-inflammatory effect by targeting PPAR-γ which inhibit production of inflammatory cytokines, such as tissue necrosis factor-alpha, interleukin-1 (IL-1) and IL-6, known as major contributors of inflammation [59,61].…”

Section: Ppar-γ and Other Pharmacodynamicsmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor-Gamma, an Emerging Potential Target to Combat Metabolic Disorder

Bairy¹

2017

Asian J Pharm Clin Res

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Day-by-day metabolic disorder/syndrome (MS) falling in love with current lifestyle status of everyone especially after study age group of people. If we look carefully around us, we will see evidence is growing up of diabetic, obese, and hypertensive population regularly. In urgencies of above view extensive literature survey has been done prioritizing prevalence of metabolic disorder and peroxisome proliferator-activated receptor-gamma (PPAR-γ) as potential target protein. This review covered current status of MS emphasizing diabetes along with its management criteria. Special importance is given to PPAR-γ exploring its metabolic regulation and structural orientation for understanding ligand-protein interaction. Development of PPAR-γ agonist thiazolidinediones (TZDs) and other pharmacodynamic importance of this nuclear receptor also discussed. Being as nuclear receptor more genomics exploitation needs to be done emphasizing minimization of cardiac adverse effect. Selective PPAR modulator (SPPRM), TZDs are the master regulator of adipogenesis and angiogenesis which makes TZD more interesting topic to explore. Developmental hierarchy suggests that in a few years from now PPAR-γ won't be in the list of double edge sword.

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The effect of peroxisome proliferator-activated receptor-γ ligand on urological cancer cells

Cited by 24 publications

References 0 publications

Telmisartan inhibits human urological cancer cell growth through early apoptosis

Telmisartan inhibits human urological cancer cell growth through early apoptosis

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

Peroxisome Proliferator-Activated Receptor-Gamma, an Emerging Potential Target to Combat Metabolic Disorder

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