Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: KEGG:D02027 (Tranilast)
205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of tranilast on DNA synthesis and cell proliferation in cultured rat mesangial cells, treated with platelet-derived growth factor (PDGF), were investigated. Tranilast significantly inhibited PDGF-stimulated DNA synthesis and cell proliferation in a dose-dependent manner. In the absence of PDGF, it also enhanced cytokine-induced nitric oxide (NO) production, PDGF significantly inhibited cytokine-induced NO production, but tranilast completely abolished this inhibitory effect of PDGF. These results show that tranilast inhibits PDGF-induced proliferation of mesangial cells under both normal and inflammatory conditions.
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PMID:Tranilast inhibits the effects of platelet-derived growth factor on cell proliferation and induction of nitric oxide. 871 31

Intimal hyperplasia is a serious problem after percutaneous transluminal coronary angioplasty (PTCA). In this study, we investigated the effects of tranilast on intimal hyperplasia in both in vivo and in vitro experiments. For the in vivo experiments, we used the balloon injury model and the cuff treatment model of rabbits fed regular chow. In the balloon injury model, tranilast decreased intimal area, intima/media ratio, stenosis ratio and vascular DNA content after endothelial injury. Also in the cuff treatment model, tranilast suppressed the intimal hyperplasia. In the in vitro experiments, we assessed the effects of tranilast on platelet-derived growth factor-induced rabbit vascular smooth muscle cell (VSMC) migration and proliferation and on collagen synthesis by VSMCs. Tranilast inhibited VSMC migration, proliferation and collagen synthesis. These results suggest that tranilast has a suppressive effect on intimal hyperplasia after a vascular injury such as PTCA.
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PMID:Tranilast suppresses intimal hyperplasia in the balloon injury model and cuff treatment model in rabbits. 877 60

1. Newborn human vascular smooth muscle cells (VSMCs) proliferated faster and were more sensitive to platelet-derived growth factor-BB (PDGF-BB) than those from adults. In this study, we investigated mechanism of the inhibitory effect of tranilast on PDGF-BB-induced proliferation of VSMCs from newborns. 2. Tranilast (30-300 microM) concentration-dependently inhibited the VSMC proliferation in randomly growing cultures stimulated with PDGF-BB. 3. Tranilast (30-300 microM) concentration-dependently inhibited the [3H]-thymidine incorporation into DNA in VSMCs that had been synchronized by 48 h serum depletion and then stimulated by addition of PDGF-BB. However, tranilast had little influence on unscheduled DNA synthesis in quiescent cells or on RNA and protein synthesis, unlike aphidicolin, actimomycin D, and cycloheximide. 4. In synchronized VSMC cultures, tranilast still inhibited the PDGF-BB-induced DNA synthesis even when added 18 h after stimulation of the quiescent cells. The mode of the antiproliferative action of tranilast was different from that of NiCl2, genistein, or staurosporin. In addition, flow cytometry of synchronized VSMCs treated with tranilast revealed a blockade of PDGF-inducible cell-cycle progression at the G1/S checkpoint. 5. Northern blotting showed that tranilast (30-300 microM) concentration-dependently suppressed constitutive c-myc mRNA expression even when added 18 h after PDGF-BB-stimulation of quiescent VSMCs. Tranilast still had an inhibitory effect on the induction of c-myc mRNA when de novo protein synthesis was inhibited by cycloheximide and did not shorten the degradation of c-myc mRNA at the post-transcriptional level, demonstrating that tranilast directly inhibited c-myc mRNA expression at the transcriptional level. 6. These results suggest that the inhibitory effect of tranilast on PDGF-BB-induced proliferation is due to S-phase blockade and may be, at least in part, involved in the direct suppression of c-myc gene expression. Tranilast did not cause cell toxicity and may therefore hold promising potential for the prevention of vascular proliferative diseases.
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PMID:Antiproliferative and c-myc mRNA suppressive effect of tranilast on newborn human vascular smooth muscle cells in culture. 879 62

The present study was conducted to establish a pharmacological method of controlling growth of vascular smooth muscle cells (VSMC) by blocking calcium entry. In cultured rat VSMC, 1 nM platelet-derived growth factor (PDGF) induced a biphasic elevation of cytoplasmic free calcium concentration, ([Ca2+]c). The second sustained phase of [Ca2+]c was dependent on extracellular calcium. At lower concentrations, PDGF induced oscillatory changes in [Ca2+]c, and reduction of extracellular calcium attenuated the oscillation. An antiallergic compound, tranilast, abolished the sustained phase of [Ca2+]c induced by 1 nM PDGF. Tranilast also inhibited the oscillatory changes in [Ca2+]c induced by 200 pM PDGF. In addition, PDGF-induced calcium influx in the late G1 phase, as assessed by measuring the initial uptake of 45Ca, was inhibited by tranilast in a concentration-dependent manner. Tranilast also inhibited PDGF-augmented DNA synthesis; the ID50 for the inhibition of DNA synthesis was nearly identical to that for calcium influx. Although tranilast blocked PDGF-induced calcium entry, it did not affect PDGF-mediated autophosphorylation of the PDGF receptor, activation of phosphatidylinositol 3-kinase, activation of Ras or mitogen-activated protein kinase. Similarly, PDGF-induced elevation of diacylglycerol was not affected by tranilast. These results suggest that the antiallergic drug tranilast inhibits PDGF-induced DNA synthesis by blocking PDGF-mediated calcium entry. Tranilast may be of use in controlling PDGF-induced DNA synthesis in VSMC.
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PMID:Blockade of DNA synthesis induced by platelet-derived growth factor by tranilast, an inhibitor of calcium entry, in vascular smooth muscle cells. 886 20

Stellate cells, the primary extracellular matrix-producing cells in the liver, undergo activation characterized by fibrogenesis, proliferation and smooth muscle alpha-actin expression, in hepatic fibrosis or when cultured on plastic. TGF beta 1 is known to have a pivotal role in fibrogenesis. Tranilast, a drug used for allergic diseases with anti-inflammatory effects, is known to inhibit collagen synthesis by cultured fibroblasts. Thus, effects of tranilast on activation and TGF beta 1 expression in stellate cells was investigated in vitro. Tranilast reduced collagen synthesis in a dose-related manner up to 50.8% of the control. This effect was reversible after tranilast withdrawal. The mobility of procollagen on gel electrophoresis and the ratio of intracellular procollagen to extracellular collagen concentrations were not affected by tranilast. Tranilast decreased DNA synthesis and increased smooth muscle alpha-actin expression. mRNA expressions of procollagen and TGF beta 1 were reduced by tranilast. Tranilast with anti-fibrogenic and anti-inflammatory actions merits consideration as a candidate for therapeutic agent of hepatic fibrosis.
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PMID:Inhibitory effect of tranilast on activation and transforming growth factor beta 1 expression in cultured rat stellate cells. 887 16

We investigated the effects of tranilast on the growth of cultured rat mesangial cells. The number of mesangial cells increased fivefold during a 5-day incubation in RPMI 1640 with 20% fetal bovine serum. The number of cells was significantly lower in the presence of tranilast than in its abscence. Tranilast (0 approximately 500 microM) inhibited platelet-derived growth factor (PDGF)-induced DNA synthesis of rat mesangial cells cultured in RPMI 1640 medium containing 0.5% fetal bovine serum in a dose-dependent manner. The inhibition of DNA synthesis by tranilast was not affected by the presence of indomethacin (1 microg/ml) or N(G)-monomethyl-L-arginine (0.5 mM). Tranilast did not stimulate nitrite oxide synthesis in PDGF-stimulated cells. Mitogen-activated protein kinase activity in mesangial cells was significantly increased by exposure to PDGF, while the effect was significantly suppressed in the presence of tranilast. The present study revealed that tranilast inhibits the growth of rat mesangial cells, independently of nitric oxide or prostacycline synthesis.
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PMID:Tranilast inhibits the growth of rat mesangial cells. 914 84

In MCF-7 breast cancer cells, insulin-like growth factor-1 (IGF-1) increased the calcium-permeability of the cells by activating a voltage-independent calcium-permeable channel. IGF-1 also induced oscillatory elevation of cytoplasmic free calcium concentration in these cells. An anti-allergic compound, tranilast, reduced the calcium-permeability augmented by IGF-1 in a dose-dependent manner and blocked the oscillatory elevation of cytoplasmic free calcium concentration. Tranilast did not affect early intracellular signals activated by IGF-1, including receptor autophosphorylation, activations of Ras, mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Tranilast inhibited increases in [3H]-thymidine incorporation, DNA content and cell number induced by IGF-1. The ID50 for [3H]-thymidine incorporation and DNA content were about 10 microM. The inhibitory effect of tranilast was reversible, and cell viability was not affected. Treatment with tranilast increased the number of cells in the G1 phase suggesting that this compound induced G1 arrest. Tranilast also reduced the phosphorylation of the retinoblastoma protein. These results indicate that tranilast inhibits the IGF-1-induced cell growth in MCF-7 cells by blocking calcium entry.
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PMID:Inhibition of proliferation of MCF-7 breast cancer cells by a blocker of Ca(2+)-permeable channel. 929 25

We have previously reported that tranilast, an anti-allergic drug, prevented the experimental intimal thickening in the rat and mouse femoral arteries and its effect may be exerted through the inhibition of vascular smooth muscle cell proliferation. However, its inhibitory mechanism has yet to be understood. In this study, we investigated the inhibitory effect of tranilast on platelet-derived growth factor BB-homodimer (PDGF-BB) mediated signal transduction pathways in cultured human coronary artery smooth muscle cells (CASMCs). Growth responses to PDGF-BB were measured by [(3)H]-thymidine incorporation or cell counting. Activation of DNA synthesis and augmentation of cell proliferation stimulated by PDGF-BB in quiescent cultures of CASMCs were inhibited by tranilast in a concentration-dependent manner. Western blot analysis of lysates from CASMCs with an anti-activated mitogen-activated protein (MAP) kinase antibody revealed that tranilast (10 - 300 microM) inhibited MAP kinase activation by PDGF-BB in a concentration-dependent manner. Tranilast also reduced PDGF-BB-stimulated tyrosine phosphorylation of a 180 kDa band, corresponding in mass to the PDGF beta-receptor, as shown by immunoblots using an anti-phosphotyrosine antibody. Receptor-binding study with [(125)I]-PDGF-BB on CASMCs showed that tranilast (10 - 1000 microM) inhibited the specific binding of PDGF-BB to cell surface receptors in a concentration-dependent manner. Scatchard analysis revealed that pretreatment with 300 microM tranilast decreased the maximum binding capacity (B(max)) from 27.6 to 18.0 fmol 10(6) cells(-1) without affecting binding affinity (K(d) approximately 0.15 nM), indicating a non-competitive inhibition of the receptor binding. These results suggest that the suppression of human CASMC growth by tranilast might be at least partly due to blockade of PDGF-BB-receptor binding.
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PMID:Inhibitory mechanism of tranilast in human coronary artery smooth muscle cells proliferation, due to blockade of PDGF-BB-receptors. 1080 67

Extensive infiltration of normal brain tissue and suppression of anti-tumor immune surveillance mediated by molecules such as transforming growth factor-beta (TGF-beta) are key biological features that contribute to the malignant phenotype of human gliomas. Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) is an anti-allergic compound used clinically to control atopic and fibrotic disorders. These effects are attributed to the suppression of TGF-beta1 synthesis and interference with growth factor-mediated proliferation and migration of fibroblasts and vascular smooth muscle cells. Here, we show that tranilast inhibits DNA synthesis and proliferation of human malignant glioma cells and promotes p21 accumulation in the absence of cytotoxicity. Further, tranilast reduces the release of TGF-beta1 and TGF-beta2 by glioma cells and inhibits migration, chemotactic responses and invasiveness. These effects are not associated with a reduction of alpha(v)beta(3) integrin expression at the cell surface but appear to involve inhibition of matrix metalloproteinase-2 expression and activity. Neither the tranilast-mediated inhibition of proliferation nor the inhibition of migration was counteracted by supplementation with exogenous TGF-beta. Finally, tranilast administered orally inhibited the growth of experimental 9L rat gliomas and reduced expression of TGF-beta2 in vivo. We conclude that tranilast might be a useful therapeutic agent for the treatment of human malignant glioma because of a TGF-beta-independent abrogation of the malignant phenotype of proliferation, migration and invasiveness and because of the antagonism of TGF-beta-associated immunosuppression.
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PMID:N-[3,4-dimethoxycinnamoyl]-anthranilic acid (tranilast) inhibits transforming growth factor-beta relesase and reduces migration and invasiveness of human malignant glioma cells. 1139 21

Tranilast has long been used clinically to treat allergic diseases such as bronchial asthma. To further clarify the antiinflammatory machanism, we examined the ability of tranilast to counteract the prolongation of eosinophil survival induced by interleukin (IL)-5. Tranilast reduced the IL-5 prolonged survival of eosinophils at the concentration range of 30 microg/ml to 100 microg/ml. The DNA extracted from eosinophils cultured with tranilast showed signs of fragmentation that was comparable with apoptosis. Electron-microscopic analysis of activated eosinophils cultured with 100 microg/ml of tranilast also revealed morphologic features of apoptosis. These data suggest that tranilast may act in vivo on activated eosinophils to reduce inflammation in allergic diseases.
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PMID:Suppressive effect of tranilast on interleukin-5 prolonged eosinophils survival via apoptosis. 1143 Apr 66


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